Original Article
Association between Tumor Necrosis Factor-α and Disease Progression in Patients with Multiple Sclerosis
N Engl J Med 1991; 325:467-472August 15, 1991
- Abstract
- Abstract
Background.
Cachectin, or tumor necrosis factor-α (TNF-α), is a principal mediator of the inflammatory response and may be important in the pathogenesis and progression of multiple sclerosis, an inflammatory disease of the central nervous system.
Methods.
In a 24-month prospective study, we used a sensitive enzyme-linked immunosorbent assay to determine levels of TNF-α in cerebrospinal fluid and serum in 32 patients with chronic progressive multiple sclerosis and in 20 with stable multiple sclerosis and 85 with other neurologic diseases. An attempt was made to relate TNF-α levels with the degree of disability of the patients with multiple sclerosis and with their neurologic deterioration during the 24 months of observation.
Results.
High levels of TNF-α were found in the cerebrospinal fluid of 53 percent of the patients with chronic progressive multiple sclerosis and in none of those with stable multiple sclerosis (P<0.001). TNF-α was detected in the cerebrospinal fluid of 7 percent of the controls (P<0.01) with other neurologic disease. In patients with chronic progressive multiple sclerosis, mean TNF-α levels were significantly higher in the cerebrospinal fluid than in corresponding serum samples (52.41 vs. 11.88 U per milliliter; range, 2 to 178 vs. 2 to 39; P<0.001). In these patients, cerebrospinal fluid levels of TNF-α correlated with the degree of disability (r = 0.834, P<0.001) and the rate of neurologic deterioration (r = 0.741, P<0.001) before the start of the study. Cerebrospinal fluid levels also correlated with the increase in neurologic disability after 24 months of observation (r = 0.873, P<0.001).
Conclusions.
These data provide evidence of intrathecal synthesis of TNF-α in multiple sclerosis and suggest that the level of TNF-α in cerebrospinal fluid correlates with the severity and progression of the disease. Our results suggest that TNF-α may reflect histologic disease activity in multiple sclerosis and could be used to monitor outcomes or responses to therapy. (N Engl J Med 1991; 325:467–72.)
Media in This Article
Figure 1
Levels of TNF-α in Cerebrospinal Fluid (•) and Serum (○) in the Study Groups.Figure 2
Relation between the TNF-α Level in Cerebrospinal Fluid and the Degree of Disability on Entry into the Study in Patients with Chronic Progressive Multiple Sclerosis.Article Activity
- Article
MULTIPLE sclerosis, an inflammatory and demyelinating disease of the central nervous system, is regarded as a major cause of neurologic disability among young adults.1 The disease follows a chronic, recurrent course and is associated with well-established immunologic aberrations that involve both B lymphocytes2 and T lymphocytes.3 Newly formed plaques in the brains of patients with multiple sclerosis have been reported to contain T lymphocytes and macrophages at their active edges.4 Both types of cell secrete cachectin, also termed tumor necrosis factor-α (TNF-α), a cytokine that has been suggested as an important mediator in several inflammatory disorders, including those affecting the central nervous system.5 6 7 TNF-α has also been shown to be capable of selectively damaging oligodendrocytes and myelin sheaths in vitro,8 a finding that may be relevant in the context of disease progression in patients with multiple sclerosis.
In an attempt to identify an in vivo correlation of TNF-α levels to the severity of disease in multiple sclerosis, we measured free TNF-α levels in samples of cerebrospinal fluid and serum from 32 patients with chronic progressive multiple sclerosis and correlated them with clinical evidence of disease progression over a period of two years. Findings were compared with those from patients with clinically stable multiple sclerosis as well as from patients with various other inflammatory and noninflammatory neurologic diseases.
Methods
Selection of Patients
The study was planned prospectively with stringent selection criteria. Patients were selected for further study if they had clinically established multiple sclerosis,9 had a chronic progressive disease with clear adherence to the originally assigned disease type, were between 20 and 50 years of age, had cerebrospinal fluid samples collected at entry and at the time of the disability assessment, were able to attend a follow-up appointment 2 years after entry into the study, and had details of the duration of the disease clearly documented in their medical notes. We excluded patients with disorders that compromised assessment of neurologic function, such as arthritis deformans, major amputations, or psychoses; patients who had other types of illnesses that could affect the outcome of the study; pregnant women or those planning to become pregnant within two years; and patients who had received treatment with steroids for one year before entry, or immunosuppressive medications or total lymphoid irradiation at any time.
Of 265 patients with multiple sclerosis who were originally considered, 32 patients with chronic progressive multiple sclerosis satisfied the preestablished selection criteria and were included in the study. They had a mean age (±SD) of 37.4±6.3 years and had had steady progression of the disorder since its onset. Their degree of disability at the time of the collection of cerebrospinal fluid was assessed with the expanded disability status scale (EDSS).10 This scale, which helps monitor the natural history of multiple sclerosis and the response to treatment, uses a scoring system with 0.5-step increments to record objective neurologic impairment; scores range from 0 (normal) to 10 (death due to multiple sclerosis).
All patients with chronic progressive multiple sclerosis were required to have objective evidence of disease progression without remission or stabilization for a minimum of one year before the study, with an increase of 1.0 or more points on the EDSS. At the beginning of the study they had EDSS scores of 3 to 6. The rate of neurologic deterioration was evaluated by the progression index,11 , 12 which is defined as the ratio of the disability status (i.e., the EDSS score) to the duration of the disease in years. This index is considered a reasonable estimate of the rate of deterioration.12 A small quotient (<0.2) means a benign course, whereas larger quotients indicate active disease (values above 1.5 indicate a malignant course). The duration of disease varied among the patients (range, 1 to 14 years), so that the EDSS and the progression index effectively measured two variables.
On the initial visit, levels of TNF-α in cerebrospinal fluid and serum were measured by an investigator who was unaware of the patients' clinical status and the degree of disability was assessed with the EDSS. The patients were then followed regularly for two years. No samples obtained before the study began were included. At the end of the study, progression-index scores and EDSS scores were determined for all patients by the same examiners who evaluated them at the beginning of the study to avoid interexaminer variability.13 The investigator who measured EDSS at the end of the study did not know the patients' TNF-α levels.
Controls
Paired samples of cerebrospinal fluid and serum were obtained from 20 patients with stable multiple sclerosis who were matched for age, sex, and the extent of disability to serve as disease controls. Paired samples were also obtained from 85 age-matched and sex-matched patients with various neurologic diseases to serve as a neurologic control group. This group consisted of 6 patients with bacterial meningitis, 3 with the acquired immunodeficiency syndrome (AIDS)—dementia complex, 7 with acute Guillain—Barré syndrome, 5 with neurosarcoidosis, 6 with cerebral lupus, 5 with myasthenia gravis, 10 with cerebrovascular accident, 8 with motor neuron disease, 5 with hereditary sensorimotor neuropathy, 10 with benign intracranial hypertension, 10 with Alzheimer's disease, 6 with Parkinson's disease, and 4 with Huntington's disease.
Assays
All assays were performed in a blinded fashion on coded sterile samples. To prevent the degradation of protein, 1000 kallikrein inhibitory units of protease inhibitor (aprotinin, Sigma) was added to each milliliter of cerebrospinal fluid and serum at the time of the sample collections. The cells were then separated by cytocentrifugation, and all samples were filtered through a 0.22-μm disposable sterile filter (Millipore) to remove contaminating paniculate materials. Samples were subsequently frozen in aliquots at — 70°C and thawed just before use.
Levels of TNF-α in native cerebrospinal fluid and diluted serum samples were measured by a sensitive sandwich-type enzyme-linked immunosorbent assay14 with a purified monoclonal antibody to human TNF-α (Chiron) and rabbit polyclonal antihuman TNF-α antibody (Genzyme). A standard curve was generated on each assay with freshly diluted standard concentrations of purified recombinant human TNF-α (Genzyme). This method can detect levels in excess of 0.01 U per milliliter, and reproducible positive results were obtained on repeated testing. One unit of TNF-α was defined as the amount of TNF-α required to mediate half-maximal cytotoxicity of L929 cells in the presence of dactinomycin.
Oligoclonal IgG bands were detected in cerebrospinal fluid by agarose isoelectric focusing.15 The amount of IgG synthesized intrathecally was calculated according to the formula of Tourtellotte and Ma,16 and the total protein content of cerebrospinal fluid was determined by the benzethonium chloride precipitation technique.17 The cerebrospinal fluid cell count was performed within six hours of the lumbar puncture; after preparation in a Shandon cytocentrifuge, cells were stained with Giemsa stain and examined.
Statistical Analysis
Confidence intervals for nonparametric data were calculated,18 and the Wilcoxon rank-sum test, Spearman rank correlation, and two-sided Mann—Whitney test were used as appropriate for statistical analysis. The relative relations of levels of TNF-α in cerebrospinal fluid to clinical and biochemical indicators in all patients with chronic progressive multiple sclerosis were tested by forward stepwise multiple logistic-regression analysis,19 with TNF-α levels in cerebrospinal fluid as the dependent variable. Log transformation was necessary because of the skewed distribution. Backward stepwise logistic-regression analyses were also performed and produced identical results in all cases. Statistical analyses were performed with SPSS/PC+ software. All P values in the study were two-tailed.
Results
Separate studies of samples not treated with aprotinin showed that the addition of the protease inhibitor improved the detectability of TNF-α in cerebrospinal fluid and serum six-fold. TNF-α was stable provided repeated thawing and refreezing of the samples was avoided.
Elevated levels of TNF-α were detected in the cerebrospinal fluid of 17 patients with chronic progressive multiple sclerosis (53 percent) and in none of the group with stable multiple sclerosis (Fig. 1Figure 1
Levels of TNF-α in Cerebrospinal Fluid (•) and Serum (○) in the Study Groups.). High cerebrospinal fluid levels of TNF-α were detected in two patients with chronic progressive multiple sclerosis in whom no serum levels were detected. Conversely, high TNF-α levels (mean, 3.8 U per milliliter) were found in serum samples from three patients with progressive disease who had no detectable levels of TNF-α in cerebrospinal fluid. In the control groups, high levels of TNF-α in cerebrospinal fluid and serum were detected in six patients (7 percent): three with bacterial meningitis, two with AIDS—dementia complex, and one with Guillain—Barré syndrome (Fig. 1). Three other patients in the control group (two with Guillain—Barré syndrome and one with AIDS—dementia complex) had detectable levels of TNF-α (mean, 14.2 U per milliliter) only in serum.In 17 patients with chronic progressive multiple sclerosis who had detectable levels of TNF-α, the mean (±SD) levels in cerebrospinal fluid were significantly higher than those in corresponding samples of serum (97.88±47.84 vs. 20.94± 10.92 U per milliliter; 95 percent confidence interval, 74.42 to 122.87 vs. 15.32 to 26.55). Cerebrospinal fluid levels of TNF-α in these patients correlated with the EDSS scores at the beginning of the study (Fig. 2Figure 2
Relation between the TNF-α Level in Cerebrospinal Fluid and the Degree of Disability on Entry into the Study in Patients with Chronic Progressive Multiple Sclerosis.) and with the progression-index values (Fig. 3Figure 3
Relation between the TNF-α Level in Cerebrospinal Fluid and the Progression Index in Patients with Chronic Progressive Multiple Sclerosis on Entry into the Study.).In the patients with chronic progressive multiple sclerosis, the relation of TNF-α levels in cerebrospinal fluid to clinical and biochemical indicators of disease progression were analyzed by multivariate regression analysis. TNF-α levels did not correlate with the presence of oligoclonal IgG bands in cerebrospinal fluid, intrathecal IgG synthesis, cerebrospinal fluid total protein, or pleocytosis (Table 1Table 1
Clinical and Biochemical Indicators in 32 Patients with Chronic Progressive Multiple Sclerosis.). TNF-α levels were correlated with the EDSS score (P<0.0005), the change in the EDSS score from the first visit to the 24-month visit (P<0.0001), and the progression-index value (P = 0.027).In the majority of patients with chronic progressive multiple sclerosis, symptoms continued to worsen during the two-year study period, whereas only two patients with stable disease had mild worsening of symptoms. There was a significant increase in the degree of disability during the 24-month period in patients with chronic progressive multiple sclerosis who had elevated cerebrospinal fluid TNF-α levels at entry (Table 2Table 2
Change in Clinical Indexes over a 24-Month Period in 32 Patients with Chronic Progressive Multiple Sclerosis.*). One patient, who had a TNF-α level of 176 U per milliliter in cerebrospinal fluid and an EDSS score of 6.0 on entry into the study, died after 22 months of follow-up. In contrast, there was no significant increase in the degree of disability in patients with progressive disease who showed no TNF-α reactivity on entry into the study (Table 2). Six patients with chronic progressive multiple sclerosis who had a decline in the EDSS score of more than 3 points were treated with steroids during the follow-up period — an approach that did not significantly alter the rate of disease progression. No patient received azathioprine or cyclophosphamide during the follow-up period.In addition to their relation to the EDSS score, high cerebrospinal fluid levels of TNF-α at the beginning of the study implied a poor prognosis, since these levels correlated with an increase in the degree of disability over the next two years (Fig. 4Figure 4
Relation between the TNF-α Level in Cerebrospinal Fluid on the First Visit and the Change in the EDSS Score from the First Visit to the 24-Month Visit.). High cerebrospinal fluid levels of TNF-α also correlated with increased EDSS scores at the 24-month visit (r = 0.873, P<0.001). Although the EDSS score correlated with the value for the progression index at entry (r = 0.741, P<0.001), the index values remained remarkably stable throughout the study period (Table 2). Nonetheless, high cerebrospinal fluid levels of TNF-α correlated with the value for the progression index at the end of the study (r = 0.851, P<0.001).Discussion
We found significantly higher levels of TNF-α in the cerebrospinal fluid of patients with chronic progressive multiple sclerosis than in patients with stable multiple sclerosis or with other neurologic diseases. Cerebrospinal fluid levels of TNF-α were also correlated with the degree of disability in patients with progressive disease, and high levels predicted a poor prognosis during a 24-month period of observation. These results support a role for TNF-α in the progression of multiple sclerosis. It has already been suggested that TNF-α has a role in the pathogenesis of demyelination.20 Cytotoxic T lymphocytes, which can produce TNF-α, are involved in the events leading to acute demyelination,4 and TNF-α was reported to cause both disruption of myelin and permanent damage to oligodendrocytes.8 Furthermore, significantly higher amounts of TNF-α were released by mitogen-stimulated cells obtained from patients with multiple sclerosis during clinical exacerbation than in those obtained from patients during remission.21
We evaluated the degree of disease progression in patients with chronic progressive multiple sclerosis by calculating the decline in the EDSS score during the study period. Although the EDSS is an inherently ordinal scale and unit changes may not be of equal importance over its entire range, the average decline in the scores reported here is clinically important by any standard. Some natural-history studies and clinical trials22 , 23 indicate that the EDSS scores change less than 1 point per year in patients with chronic progressive multiple sclerosis. To minimize the number of patients whose conditions stabilized spontaneously during the study period, we adopted more demanding selection criteria than those used in previous studies.24 , 25 These strict entry requirements served to select patients with active disease, whose EDSS scores during the study period declined by an average of more than 2 points. Other studies that employed similarly stringent criteria26 27 28 also reported an increase in the EDSS score of 2 or more points (up to 4) during a follow-up period of 18 to 30 months.
It is important to note that each grade of disease disability in the study patients with multiple sclerosis was associated with a reasonable distribution of observed TNF-α concentrations, with no major overlap between individual grades. This fact, coupled with the significant correlations, suggests that TNF-α may be an indicator of disease progression in patients with multiple sclerosis. Whether TNF-α is directly involved in the progression of multiple sclerosis or merely reflects other basic processes is unclear. However, TNF-α causes severe damage to human endothelial cells29 and induces vascular "leak" syndrome30 —effects that may be relevant to disease progression in multiple sclerosis. Experimental, pathological, and imaging data suggest that a fundamental feature of lesions in active multiple sclerosis is local breakdown of the endothelial barriers, particularly the blood–brain barrier.31 32 33 The principal inflammatory process in this disease usually occurs around blood vessels, with only scanty inflammatory activity in the brain parenchyma.34 Macrophages, which are abundant in all acute perivascular brain lesions,34 are the most potent producers of TNF-α. The perivascular infiltrate in brain lesions in multiple sclerosis also contains activated lymphocytes, which can produce TNF-α.
Our finding that the cerebrospinal fluid of patients with chronic progressive multiple sclerosis had significantly higher levels of TNF-α than did corresponding serum samples suggests that this cytokine is released locally in the intrathecal compartment. The lack of correlation between the presence of pleocytosis and TNF-α levels suggests that TNF-α may be derived from the central nervous system and not cerebrospinal fluid cells. Production of TNF-α by the central nervous system may result from its release by macrophages and T lymphocytes, which are abundant in brain lesions due to multiple sclerosis, as well as by astrocytes and microglial cells.35 , 36 TNF-α has been detected in astrocytes in brain tissues of patients with multiple sclerosis.37 The failure to detect TNF-α in the cerebrospinal fluid of patients with multiple sclerosis in another study38 may have been due to differences in the way patients were selected or to the instability of TNF-α if it is not treated with a protease inhibitor. In addition, the ability to detect TNF-α depends on the particular assay used, since different procedures have been shown to vary significantly in their sensitivity and limits of detection.39 Our demonstration of a significant increase in TNF-α levels in cerebrospinal fluid relative to levels in serum has been corroborated by a recent independent study.40
We found no correlation of neurologic impairment with serum TNF-α levels in patients with multiple sclerosis. This finding raises the possibility that intrathecal concentrations of TNF-α are more important than systemic levels in the clinical progression, and perhaps histologic activity, of multiple sclerosis. Because this study was blinded, we were unaware of the clinical importance of TNF-α levels in cerebrospinal fluid during the follow-up period. Thus, repeated collections of cerebrospinal fluid samples were not ethically justified. However, repeated measurements are indicated to evaluate how changes in TNF-α levels may be correlated with changes in the trajectory of the disease. Similarly, further studies will be required to elucidate the interactions of TNF-α and other cytokines, such as lymphotoxin, in the progression of multiple sclerosis.
The findings presented here may have important prognostic and therapeutic implications. A test based on cerebrospinal fluid analysis that can predict the progression of multiple sclerosis could be regarded as a marker of activity and would be of great importance in monitoring outcome. The removal of TNF-α41 or neutralization of its effect42 , 43 might be of benefit in patients with chronic progressive multiple sclerosis.
We are indebted to June Smalley, who tirelessly developed and appended computer data-base files while blinded to clinical and pathologic data; to Naghat Lakdawala for preparing and coding the samples while blinded to clinical information; to Magenlal Chowhan for detecting oligoclonal IgG bands; and to the neurologists who allowed us to obtain clinical data on their patients.
Source Information
From the Department of Clinical Neurochemistry, Institute of Neurology, the National Hospital for Neurology and Neurosurgery, London (M.K.S.), and the Department of Neuro-Psychiatry, Free University of Brussels, Brussels, Belgium (R.H.). Address reprint requests to Dr. Sharief at the Institute of Neurology, the National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom.
- References
References
1
Ebers GC. Multiple sclerosis and other demyelinating diseases. In: Asbury AK, McKhann GM, McDonald WI, eds. Diseases of the nervous system. Philadelphia: Ardmore Medical Books, 1986:1268–81.
2
Tourtellotte
CrossRef | Web of Science | Medline3
Waksman
Web of Science | Medline4
Hauser
CrossRef | Web of Science | Medline5
Mustafa
CrossRef | Medline6
Mustafa
CrossRef | Web of Science | Medline7
Mintz
Web of Science | Medline8
Selmaj
CrossRef | Web of Science | Medline9
Poser
CrossRef | Web of Science | Medline10
Kurtzke
Web of Science | Medline11
Jersild
CrossRef | Web of Science | Medline12
Poser
CrossRef | Web of Science | Medline13
Noseworthy
Web of Science | Medline14
Michie
Full Text | Web of Science | Medline15
Walker
CrossRef | Web of Science | Medline16
Tourtellotte
Web of Science | Medline17
Luxton
Web of Science | Medline18
Campbell
CrossRef | Web of Science | Medline19
McCullagh P, Nelder JA. Generalized linear models. London: Chapman & Hall, 1983:99–106.
20
Brosnan
CrossRef | Web of Science | Medline21
Beck
CrossRef | Web of Science | Medline22
The Multiple Sclerosis Study Group.
CrossRef | Web of Science | Medline23
The Canadian Cooperative Multiple Sclerosis Study Group.
Web of Science | Medline24
Hauser
Full Text | Web of Science | Medline25
Khatri
Web of Science | Medline26
Goodkin
Web of Science | Medline27
Trotter
CrossRef | Web of Science | Medline28
Gallo
CrossRef | Web of Science | Medline29
Slungaard
CrossRef | Web of Science | Medline30
Tracey
CrossRef | Web of Science31
James
CrossRef | Web of Science | Medline32
Kermode
CrossRef | Web of Science | Medline33
Gay
CrossRef | Web of Science | Medline34
Adams
CrossRef | Web of Science | Medline35
Chung
Web of Science | Medline36
Robbins
Web of Science | Medline37
Hofman
CrossRef | Web of Science38
Franciotta
CrossRef | Web of Science | Medline39
McLaughlin
CrossRef | Web of Science | Medline40
Maimone
CrossRef | Web of Science | Medline41
Bjorvatn
CrossRef | Web of Science | Medline42
Tracey
CrossRef | Web of Science | Medline43
Robertson
Web of Science | Medline
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CrossRef13
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CrossRef14
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CrossRef17
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CrossRef20
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CrossRef25
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Elliot M. Frohman, Todd Eagar, Nancy Monson, Olaf Stuve, Nitin Karandikar. (2008) Immunologic Mechanisms of Multiple Sclerosis. Neuroimaging Clinics of North America 18:4, 577-588
CrossRef39
Saša Šega, Alenka Horvat, Uroš Rot, Branka Wraber, Alojz Ihan. (2008) Could cytokines levels or adhesion molecules expression be predictor of IFN-β treatment response in multiple sclerosis patients?. Clinical Neurology and Neurosurgery 110:9, 947-950
CrossRef40
Wayne Chadwick, Tim Magnus, Bronwen Martin, Aleksander Keselman, Mark P. Mattson, Stuart Maudsley. (2008) Targeting TNF-α receptors for neurotherapeutics. Trends in Neurosciences 31:10, 504-511
CrossRef41
Sreeram V. Ramagopalan, Gabriele C. DeLuca, Alexandra Degenhardt, George C. Ebers. (2008) The genetics of clinical outcome in multiple sclerosis. Journal of Neuroimmunology 201-202, 183-199
CrossRef42
Olga Barca, José A. Costoya, Rosa M. Señarís, Víctor M. Arce. (2008) Interferon-β protects astrocytes against tumour necrosis factor-induced apoptosis via activation of p38 mitogen-activated protein kinase. Experimental Cell Research 314:11-12, 2231-2237
CrossRef43
Jan Lin, David Ziring, Sheetal Desai, Sungjin Kim, Maida Wong, Yael Korin, Jonathan Braun, Elaine Reed, David Gjertson, Ram Raj Singh. (2008) TNFα blockade in human diseases: An overview of efficacy and safety. Clinical Immunology 126:1, 13-30
CrossRef44
Marlon P. Quinones, Yogeshwar Kalkonde, Carlos A. Estrada, Fabio Jimenez, Robert Ramirez, Lenin Mahimainathan, Srinivas Mummidi, Goutam G. Choudhury, Hernan Martinez, Lisa Adams, Matthias Mack, Robert L. Reddick, Shivani Maffi, Sylva Haralambous, Lesley Probert, Sunil K. Ahuja, Seema S. Ahuja. (2008) Role of astrocytes and chemokine systems in acute TNFα induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-κB and Akt. Molecular and Cellular Neuroscience 37:1, 96-109
CrossRef45
Ioana R. Moldovan, Anne C. Cotleur, Natacha Zamor, Robert S. Butler, Clara M. Pelfrey. (2008) Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens. Journal of Neuroimmunology 193:1-2, 161-169
CrossRef46
Laurence S. Harbige, Mohammad K. Sharief. (2007) Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis. British Journal of Nutrition 98:S1,
CrossRef47
Guangwu Xu, Yufang Shi. (2007) Apoptosis signaling pathways and lymphocyte homeostasis. Cell Research 17:9, 759-771
CrossRef48
Tania Kümpfel, Lisa-Ann Hoffmann, Heike Rübsamen, Walter Pöllmann, Wolfgang Feneberg, Reinhard Hohlfeld, Peter Lohse. (2007) Late-onset tumor necrosis factor receptor–associated periodic syndrome in multiple sclerosis patients carrying theTNFRSF1A R92Q mutation. Arthritis & Rheumatism 56:8, 2774-2783
CrossRef49
Przemyslaw J. Kotyla, Bogna Sliwinska-Kotyla, Eugene J. Kucharz. (2007) Treatment with infliximab may contribute to the development of peripheral neuropathy among the patients with rheumatoid arthritis. Clinical Rheumatology 26:9, 1595-1596
CrossRef50
THOMAS SCHMITZ, AXEL HEEP, FLORIS GROENENDAAL, DIETER H??SEMAN, SUSANNE KIE, PETER BARTMANN, MICHAEL OBLADEN, URSULA FELDERHOFF-M??SER. (2007) Interleukin-1??, Interleukin-18, and Interferon-?? Expression in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus???Markers of White Matter Damage?. Pediatric Research PAP,
CrossRef51
Alberto Romero-Mat??, Carmen Garc??a-Donoso, Susana C??rdoba-Guijarro. (2007) Efficacy and Safety of Etanercept in Psoriasis/Psoriatic Arthritis. American Journal of Clinical Dermatology 8:3, 143-155
CrossRef52
Makoto Tanno, Ichiro Nakamura, Shunsuke Kobayashi, Kumiko Kurihara, Katsumi Ito. (2006) New-onset demyelination induced by infliximab therapy in two rheumatoid arthritis patients. Clinical Rheumatology 25:6, 929-933
CrossRef53
Sheetal B. Desai, Daniel E. Furst. (2006) Problems encountered during anti-tumour necrosis factor therapy. Best Practice & Research Clinical Rheumatology 20:4, 757-790
CrossRef54
Rachel D. Wheeler, Simone P. Zehntner, Lisa M. Kelly, Lyne Bourbonniere, Trevor Owens. (2006) Elevated interferon gamma expression in the central nervous system of tumour necrosis factor receptor 1-deficient mice with experimental autoimmune encephalomyelitis. Immunology 0:0, 060616085813001-???
CrossRef55
M. Comabella, C. Romera, M. Camiña, H. Perkal, M. A. Moro, J. C. Leza, I. Lizasoain, M. Castillo, X. Montalban. (2006) TNF–α converting enzyme (TACE) protein expression in different clinical subtypes of multiple sclerosis. Journal of Neurology 253:6, 701-706
CrossRef56
Jacob H. Chung, Gregory P. Van Stavern, Larry P. Frohman, Roger E. Turbin. (2006) Adalimumab-associated optic neuritis. Journal of the Neurological Sciences 244:1-2, 133-136
CrossRef57
Adil Javed, Anthony T. Reder. (2006) Therapeutic role of beta-interferons in multiple sclerosis. Pharmacology & Therapeutics 110:1, 35-56
CrossRef58
Robert Zivadinov, Davide Nasuelli, Maria Antonietta Tommasi, Maurizia Serafin, Alessio Bratina, Maja Ukmar, Istvan Pirko, Aaron J. Johnson, Christina Furlan, Roberto S. Pozzi-Mucelli, Luisa Monti-Bragadin, Attilio Grop, Massimo Zambon, Rodolfo M. Antonello, Giuseppe Cazzato, Marino Zorzon. (2006) Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients. Neurological Research 28:3, 262-269
CrossRef59
Jose L S??nchez Carazo, Laura Mahiques Santos, Vicente Oliver Martinez. (2006) Safety of Etanercept in Psoriasis. Drug Safety 29:8, 675-685
CrossRef60
Lawrence Steinman, Scott S. Zamvil. (2005) Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends in Immunology 26:11, 565-571
CrossRef61
Snejina Mihailova, Milena Ivanova, Anastassia Mihaylova, Ludmila Quin, Olia Mikova, Elissaveta Naumova. (2005) Pro- and anti-inflammatory cytokine gene polymorphism profiles in Bulgarian multiple sclerosis patients. Journal of Neuroimmunology 168:1-2, 138-143
CrossRef62
Jongseok Lee, Sooan Shin, Ching-Hao Teng, Suk Jin Hong, Kwang Sik Kim. (2005) FimH adhesin of Escherichia coli K1 type 1 fimbriae activates BV-2 microglia. Biochemical and Biophysical Research Communications 334:3, 917-923
CrossRef63
Malabendu Jana, Kalipada Pahan. (2005) Redox regulation of cytokine-mediated inhibition of myelin gene expression in human primary oligodendrocytes. Free Radical Biology and Medicine 39:6, 823-831
CrossRef64
J K Dyer, J A Bourque, J D Steeves. (2005) The role of complement in immunological demyelination of the mammalian spinal cord. Spinal Cord 43:7, 417-425
CrossRef65
Brandon A. Miller, Fang Sun, Randolph N. Christensen, Adam R. Ferguson, Jacqueline C. Bresnahan, Michael S. Beattie. (2005) A Sublethal Dose of TNFα Potentiates Kainate-Induced Excitotoxicity in Optic Nerve Oligodendrocytes. Neurochemical Research 30:6-7, 867-875
CrossRef66
Sarah B. Khan, H. Terence Cook, Gurjeet Bhangal, Jennifer Smith, Frederick W.K. Tam, Charles D. Pusey. (2005) Antibody blockade of TNF-alpha reduces inflammation and scarring in experimental crescentic glomerulonephritis. Kidney International 67:5, 1812-1820
CrossRef67
Peter Lamprecht. (2005) TNF-α inhibitors in systemic vasculitides and connective tissue diseases. Autoimmunity Reviews 4:1, 28-34
CrossRef68
Lynne Shinto, Carlo Calabrese, Cynthia Morris, Shannon Sinsheimer, Dennis Bourdette. (2004) Complementary and Alternative Medicine in Multiple Sclerosis: Survey of Licensed Naturopaths. The Journal of Alternative and Complementary Medicine 10:5, 891-897
CrossRef69
Takeshi Oki, Shunji Takahashi, Satoshi Kuwabara, Yasumasa Yoshiyama, Masahiro Mori, Takamichi Hattori, Nobuo Suzuki. (2004) Increased ability of peripheral blood lymphocytes to degrade laminin in multiple sclerosis. Journal of the Neurological Sciences 222:1-2, 7-11
CrossRef70
Jian Hong, Ying C.Q Zang, George Hutton, Victor M Rivera, Jingwu Z Zhang. (2004) Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis. Journal of Neuroimmunology 152:1-2, 126-139
CrossRef71
Mark C Genovese, Joel M Kremer. (2004) Treatment of rheumatoid arthritis with etanercept. Rheumatic Disease Clinics of North America 30:2, 311-328
CrossRef72
John J. Bright, Chandramohan Natarajan, Subramaniam Sriram, Gladson Muthian. (2004) Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of microglia. Glia 45:2, 188-196
CrossRef73
Anat Achiron, Mathilda Mandel. (2004) T-cell vaccination in multiple sclerosis. Autoimmunity Reviews 3:1, 25-32
CrossRef74
Shin Hisahara, Hideyuki Okano, Masayuki Miura. (2003) Caspase-mediated oligodendrocyte cell death in the pathogenesis of autoimmune demyelination. Neuroscience Research 46:4, 387-397
CrossRef75
Andrzej R. Glabinski, Bartosz Bielecki, Pawel Kolodziejski, Yulong Han, Krzysztof Selmaj, Richard M. Ransohoff. (2003) TNF-α Microinjection Upregulates Chemokines and Chemokine Receptors in the Central Nervous System Without Inducing Leukocyte Infiltration. Journal of Interferon & Cytokine Research 23:8, 457-466
CrossRef76
Scott C. Foster, Crystal Daniels, Dennis N. Bourdette, Bruce F. Bebo. (2003) Dysregulation of the hypothalamic–pituitary–gonadal axis in experimental autoimmune encephalomyelitis and multiple sclerosis. Journal of Neuroimmunology 140:1-2, 78-87
CrossRef77
Robert A. Pon, Mark S. Freedman. (2003) Study of Herpesvirus saimiri immortalization of γδ T cells derived from peripheral blood and CSF of multiple sclerosis patients. Journal of Neuroimmunology 139:1-2, 119-132
CrossRef78
Munire Kilinc, Isil Saatci-Cekirge, Rana Karabudak. (2003) Serial Analysis of Soluble Intercellular Adhesion Molecule-1 Level in Relapsing-Remitting Multiple Sclerosis Patients During IFN- β 1b Treatment. Journal of Interferon & Cytokine Research 23:3, 127-133
CrossRef79
Tae Y. Yune, Mi J. Chang, Sun J. Kim, Young B. Lee, Song W. Shin, Hyewhon Rhim, Young C. Kim, Moon L. Shin, Young J. Oh, Ching T. Han, George J. Markelonis, Tae H. Oh. (2003) Increased Production of Tumor Necrosis Factor- α Induces Apoptosis after Traumatic Spinal Cord Injury in Rats. Journal of Neurotrauma 20:2, 207-219
CrossRef80
Jacques P Zappulla, Michel Arock, Lennart T Mars, Roland S Liblau. (2002) Mast cells: new targets for multiple sclerosis therapy?. Journal of Neuroimmunology 131:1-2, 5-20
CrossRef81
Payam Rezaie, Andrew Dean. (2002) Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system. Neuropathology 22:3, 106-132
CrossRef82
G.V McDonnell, S.A Hawkins. (2002) Primary progressive multiple sclerosis: increasing clarity but many unanswered questions. Journal of the Neurological Sciences 199:1-2, 1-15
CrossRef83
M. PASHENKOV, M. SÖDERSTRÖM, Y.-M. HUANG & H. LINK. (2002) Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells. Clinical & Experimental Immunology 128:2, 379-387
CrossRef84
J. Kraus, B. S. Kuehne, J. Tofighi, P. Frielinghaus, E. Stolz, F. Blaes, C. Laske, B. Engelhardt, H. Traupe, M. Kaps, P. Oschmann. (2002) Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis. Acta Neurologica Scandinavica 105:4, 300-308
CrossRef85
Ying C.Q Zang, Jyotsnabaran B Halder, Jian Hong, Victor M Rivera, Jingwu Z Zhang. (2002) Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-κB. Journal of Neuroimmunology 124:1-2, 106-114
CrossRef86
Xuan Feng, Douglas Yau, Christopher Holbrook, Anthony T. Reder. (2002) Type I Interferons Inhibit Interleukin-10 Production in Activated Human Monocytes and Stimulate IL-10 in T Cells: Implications for Th1-Mediated Diseases. Journal of Interferon & Cytokine Research 22:3, 311-319
CrossRef87
Carla Iarlori, Marcella Reale, Giovanna De Luca, Angelo Di Iorio, Claudio Feliciani, Antonio Tulli, Pio Conti, Domenico Gambi, Alessandra Lugaresi. (2002) Interferon β-1b modulates MCP-1 expression and production in relapsing–remitting multiple sclerosis. Journal of Neuroimmunology 123:1-2, 170-179
CrossRef88
M. K. Sharief. (2002) Heightened intrathecal release of soluble CD137 in patients with multiple sclerosis. European Journal of Neurology 9:1, 49-54
CrossRef89
Patrice H. Lalive, Pierre R. Burkhard, Michel Chofflon. (2002) TNF-a and psychologically stressful events in healthy subjects: Potential relevance for multiple sclerosis relapse.. Behavioral Neuroscience 116:6, 1093-1097
CrossRef90
Niveditha Mohan, Evelyne T. Edwards, Thomas R. Cupps, Patrick J. Oliverio, Glenn Sandberg, Heidi Crayton, John R. Richert, Jeffrey N. Siegel. (2001) Demyelination occurring during anti-tumor necrosis factor ? therapy for inflammatory arthritides. Arthritis & Rheumatism 44:12, 2862-2869
CrossRef91
Lesley Probert, Katerina Akassoglou. (2001) Glial expression of tumor necrosis factor in transgenic animals: How do these models reflect the “normal situation”?. Glia 36:2, 212-219
CrossRef92
Lawrence Steinman. (2001) Immunotherapy of multiple sclerosis: the end of the beginning. Current Opinion in Immunology 13:5, 597-600
CrossRef93
William H. Robinson, Mark C. Genovese, Larry W. Moreland. (2001) Demyelinating and neurologic events reported in association with tumor necrosis factor ? antagonism: By what mechanisms could tumor necrosis factor ? antagonists improve rheumatoid arthritis but exacerbate multiple sclerosis?. Arthritis & Rheumatism 44:9, 1977-1983
CrossRef94
Klaus-Peter Wandinger, Claus-Steffen St
rzebecher, Bibiana Bielekova, Greg Detore, Andreas Rosenwald, Louis M. Staudt, Henry F. McFarland, Roland Martin. (2001) Complex immunomodulatory effects of interferon-? in multiple sclerosis include the upregulation of T helper 1-associated marker genes. Annals of Neurology 50:3, 349-357
CrossRef95
J. Jensen, M. Krakauer, F. Sellebjerg. (2001) Increased T cell expression of CD154 (CD40-ligand) in multiple sclerosis. European Journal of Neurology 8:4, 321-328
CrossRef96
P Sarchielli. (2001) EXPRESSION OF TNF-α mRNA BY PERIPHERAL BLOOD MONONUCLEAR CELLS OF MULTIPLE SCLEROSIS PATIENTS TREATED WITH IFN-β 1A. Cytokine 14:5, 294-298
CrossRef97
James B. Johnston, Claudia Silva, Guido Gonzalez, Janet Holden, Kennith G. Warren, Luanne M. Metz, Christopher Power. (2001) Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis. Annals of Neurology 49:5, 650-658
CrossRef98
G. Kassiotis, G. Kollias. (2001) Uncoupling the Proinflammatory from the Immunosuppressive Properties of Tumor Necrosis Factor (Tnf) at the P55 TNF Receptor Level: Implications for Pathogenesis and Therapy of Autoimmune Demyelination. Journal of Experimental Medicine 193:4, 427-434
CrossRef99
Marie-Luise Brennan, Amitabh Gaur, Anil Pahuja, Aldons J. Lusis, Wanda F. Reynolds. (2001) Mice lacking myeloperoxidase are more susceptible to experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 112:1-2, 97-105
CrossRef100
Young B. Lee, Tae Y. Yune, Seoung Y. Baik, Young H. Shin, Shen Du, Hyewhon Rhim, Eunhee B. Lee, Young C. Kim, Moon L. Shin, George J. Markelonis, Tae H. Oh. (2000) Role of Tumor Necrosis Factor-α in Neuronal and Glial Apoptosis after Spinal Cord Injury. Experimental Neurology 166:1, 190-195
CrossRef101
Fabrizio Condorelli, Maria Angela Sortino, Anna Maria Giuffrida Stella, Pier Luigi Canonico. (2000) Relative Contribution of Different Receptor Subtypes in the Response of Neuroblastoma Cells to Tumor Necrosis Factor-α. Journal of Neurochemistry 75:3, 1172-1179
CrossRef102
K Pahan. (2000) Activation of nuclear factor-kB in the spinal cord of experimental allergic encephalomyelitis. Neuroscience Letters 287:1, 17-20
CrossRef103
Maria Cristina Morganti-Kossmann, Viviane I. Otto, Philip F. Stahel, Thomas Kossmann. (2000) The role of inflammation in neurologic disease. Current Opinion in Critical Care 6:2, 98-109
CrossRef104
Violetta Zujovic, Jes
CrossRef105
Tobias Strunk, Stefanie Bubel, Beate Mascher, Peter Schlenke, Holger Kirchner, Klaus-Peter Wandinger. (2000) Increased numbers of CCR5+ interferon-?- and tumor necrosis factor-?-secreting T lymphocytes in multiple sclerosis patients. Annals of Neurology 47:2, 269-273
CrossRef106
James F. Clapp III, Wieland Kiess. (2000) Effects of pregnancy and exercise on concentrations of the metabolic markers tumor necrosis factor α and leptin. American Journal of Obstetrics and Gynecology 182:2, 300-306
CrossRef107
Marianne Kipper-Galperin, Ruth Galilly, Haim D Danenberg, Talma Brenner. (1999) Dehydroepiandrosterone selectively inhibits production of tumor necrosis factor α and Interlukin-6 in astrocytes. International Journal of Developmental Neuroscience 17:8, 765-775
CrossRef108
M.E Duddy, M.A Armstrong, A.D Crockard, S.A Hawkins. (1999) Changes in plasma cytokines induced by interferon-β1a treatment in patients with multiple sclerosis. Journal of Neuroimmunology 101:1, 98-109
CrossRef109
Stefano Sotgiu, Maura Pugliatti, Caterina Serra, Giulio Rosati, Antonina Dolei, Maria Giovanna Marrosu. (1999) Tumor necrosis factor 2 allele does not contribute to increased tumor necrosis factor-? production in Sardinian multiple sclerosis. Annals of Neurology 46:5, 799-800
CrossRef110
Lawrence Steinman. (1999) Assessment of Animal Models for MS and Demyelinating Disease in the Design of Rational Therapy. Neuron 24:3, 511-514
CrossRef111
Eli Silber, Mohammad K Sharief. (1999) Axonal degeneration in the pathogenesis of multiple sclerosis. Journal of the Neurological Sciences 170:1, 11-18
CrossRef112
Mary E. Smith, Nancy L. Eller, Henry F. McFarland, Michael K. Racke, Cedric S. Raine. (1999) Age Dependence of Clinical and Pathological Manifestations of Autoimmune Demyelination. The American Journal of Pathology 155:4, 1147-1161
CrossRef113
Yu-Min Huang, Bao-Guo Xiao, Volkan Özenci, Mathilde Kouwenhoven, Natalia Teleshova, Sten Fredrikson, Hans Link. (1999) Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines. Journal of Neuroimmunology 99:1, 82-90
CrossRef114
Mark W. Craighead, Priyanka Tiwari, Robert G. Keynes, Catherine M. Waters. (1999) Human oligodendroglial cell line, MO3.13, can be protected from apoptosis using the general caspase inhibitor zVAD-FMK. Journal of Neuroscience Research 57:2, 236-243
CrossRef115
P. Kivisäkk, L. Stawiarz, D. Matusevicius, S. Fredrikson, M. Söderström, T. Hindmarsh, H. Link. (1999) High numbers of perforin mRNA expressing CSF cells in multiple sclerosis patients with gadolinium-enhancing brain MRI lesions. Acta Neurologica Scandinavica 100:1, 18-24
CrossRef116
Constantinos Petrovas, Spiros M Daskas, Evriklia S Lianidou. (1999) Determination of tumor necrosis factor-α (TNF-α) in serum by a highly sensitive enzyme amplified lanthanide luminescence immunoassay. Clinical Biochemistry 32:4, 241-247
CrossRef117
George Kollias, Eleni Douni, George Kassiotis, Dimitris Kontoyiannis. (1999) On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Immunological Reviews 169:1, 175-194
CrossRef118
A. H. H. Van Boxel-Dezaire, S. C. J. Hoff, B. W. Van Oosten, C. L. Verweij, A. M. Dräger, H. J. Adèr, J. C. Van Houwelingen, F. Barkhof, C. H. Polman, L. Nagelkerken. (1999) Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis. Annals of Neurology 45:6, 695-703
CrossRef119
H Jiang, B Bielekova, H Okazaki, K Clarence-Smith, K.P Johnson, G Bergey, R Martin, S Dhib-Jalbut. (1999) The effect of vesnarinone on TNFα production in human peripheral blood mononuclear cells and microglia: a preclinical study for the treatment of multiple sclerosis. Journal of Neuroimmunology 97:1-2, 134-145
CrossRef120
Michael S. Dobbie, Roger D. Hurst, Nigel J. Klein, Robert A.H. Surtees. (1999) Upregulation of intercellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-α in an in vitro model of the blood–brain barrier. Brain Research 830:2, 330-336
CrossRef121
M. Mayne, P. N. Shepel, Y. Jiang, J. D. Geiger, C. Power. (1999) Dysregulation of adenosine A1 receptor-mediated cytokine expression in peripheral blood mononuclear cells from multiple sclerosis patients. Annals of Neurology 45:5, 633-639
CrossRef122
MICHAEL MAYNE, WEIMIN NI, RACHEL McKENNA, CHRISTOPHER POWER. (1999) Antisense Oligodeoxynucleotides Targeting Internal Exon Sequences Efficiently Regulate TNF-α Expression. Antisense and Nucleic Acid Drug Development 9:2, 135-144
CrossRef123
D.F. Horrobin, C.N. Bennett. (1999) Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis Possible candidate genes. Prostaglandins, Leukotrienes and Essential Fatty Acids 60:4, 217-234
CrossRef124
Karen S. Mark, Donald W. Miller. (1999) Increased permeability of primary cultured brain microvessel endothelial cell monolayers following TNF-α exposure. Life Sciences 64:21, 1941-1953
CrossRef125
T. Nagy, T. J´nossy, C. Vizler, K. Bohus, F. Jóa, P. Végh, E. Duda. (1999) Pathophysiological effects of human TNF-alpha-producing tumor xenografts in immunosuppressed mice. APMIS 107:7-12, 903-912
CrossRef126
M.A Kahn, J.M Dopp, S Liva, A.J MacKenzie-Graham, R Chang, A Huang, R Nazarian, P Dell'Albani, D Condorelli, R.R Voskuhl, J de Vellis. (1999) Temporal kinetics and cellular phenotype of TNF p55/p75 receptors in experimental allergic encephalomyelitis. Journal of Neuroimmunology 95:1-2, 19-34
CrossRef127
Tomas Bergström. (1999) Herpesviruses—a rationale for antiviral treatment in multiple sclerosis. Antiviral Research 41:1, 1-19
CrossRef128
Antonino Uncini, Antonio Di Muzio, Giovanni Di Guglielmo, Maria Vittoria De Angelis, Giovanna De Luca, Alessandra Lugaresi, Domenico Gambi. (1999) Effect of rhTNF-α injection into rat sciatic nerve. Journal of Neuroimmunology 94:1-2, 88-94
CrossRef129
C. Guillen, A. Prieto, J. C. Alvarez-Cermeño, M. de la Piedra, A. Gimeno, M. Alvarez-Mon. (1999) Regulatory Effects of Cytokines and Cyclosporine A on Peripheral Blood Mononuclear Cs from Stable Multiple Sclerosis Patients. Immunopharmacology and Immunotoxicology 21:3, 527-549
CrossRef130
Talma Brenner, Enrique Poradosu, Dov Soffer, Camille Sicsic, Aviv Gazit, Alexander Levitzki. (1998) Suppression of Experimental Autoimmune Encephalomyelitis by Tyrphostin AG-556. Experimental Neurology 154:2, 489-498
CrossRef131
Ariel Miller, Sarah Shapiro, Rosa Gershtein, Amalia Kinarty, Hanna Rawashdeh, Silvia Honigman, Nitza Lahat. (1998) Treatment of multiple sclerosis with Copolymer-1 (Copaxone®): implicating mechanisms of Th1 to Th2/Th3 immune-deviation. Journal of Neuroimmunology 92:1-2, 113-121
CrossRef132
Philippe Monteyne, Benoit Guillaume, Christian J.M Sindic. (1998) B7-1 (CD80), B7-2 (CD86), interleukin-12 and transforming growth factor-β mRNA expression in CSF and peripheral blood mononuclear cells from multiple sclerosis patients. Journal of Neuroimmunology 91:1-2, 198-203
CrossRef133
M Angeles Muñoz-Fernández, Manuel Fresno. (1998) The role of tumour necrosis factor, interleukin 6, interferon-γ and inducible nitric oxide synthase in the development and pathology of the nervous system. Progress in Neurobiology 56:3, 307-340
CrossRef134
Katerina Akassoglou, Jan Bauer, George Kassiotis, Manolis Pasparakis, Hans Lassmann, George Kollias, Lesley Probert. (1998) Oligodendrocyte Apoptosis and Primary Demyelination Induced by Local TNF/p55TNF Receptor Signaling in the Central Nervous System of Transgenic Mice. The American Journal of Pathology 153:3, 801-813
CrossRef135
Peter-Brian Andersson, Donald E Goodkin. (1998) Glucocorticosteroid therapy for multiple sclerosis: A critical review. Journal of the Neurological Sciences 160:1, 16-25
CrossRef136
Nicole Kerlero de Rosbo, Avraham Ben-Nun. (1998) T-cell Responses to Myelin Antigens in Multiple Sclerosis; Relevance of the Predominant Autoimmune Reactivity to Myelin Oligodendrocyte Glycoprotein. Journal of Autoimmunity 11:4, 287-299
CrossRef137
P.A Calabresi, L.R Tranquill, H.F McFarland, E.P Cowan. (1998) Cytokine gene expression in cells derived from CSF of multiple sclerosis patients. Journal of Neuroimmunology 89:1-2, 198-205
CrossRef138
Christina Larsson, Christina Bernström-Lundberg, Staffan Edström, Tomas Bergström. (1998) Tumor necrosis factor-α response and herpesvirus infection in bell's palsy. The Laryngoscope 108:8, 1171-1176
CrossRef139
Wolfgang Liedtke, Barbara Cannella, Richard J. Mazzaccaro, John M. Clements, Karen M. Miller, Kai W. Wucherpfenning, Andrew J. H. Gearing, Cedric S. Raine. (1998) Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors. Annals of Neurology 44:1, 35-46
CrossRef140
Kiyoto Hohnoki, Atsushi Inoue, Chang-Sung Koh. (1998) Elevated serum levels of IFN-γ, IL-4 and TNF-α/unelevated serum levels of IL-10 in patients with demyelinating diseases during the acute stage. Journal of Neuroimmunology 87:1-2, 27-32
CrossRef141
Krzysztof Selmaj, Agata Walczak, Marcin Mycko, Tomasz Berkowicz, Tadahiko Kohno, Cedric S. Raine. (1998) Suppression of experimental autoimmune encephalomyelitis with a TNF binding protein (TNFbp) correlates with down-regulation of VCAM-1/VLA-4. European Journal of Immunology 28:6, 2035-2044
CrossRef142
Tomohisa Fushimi, Atsushi Inoue, Chang-Sung Koh, Masashi Yamazaki, Yoshihiro Ishihara, Byung S. Kim. (1998) The Effect of Pentoxifylline (PTX) on Theiler's Murine Encephalomyelitis Virus (TMEV)-Induced Demyelinating Disease. Cellular Immunology 186:2, 140-146
CrossRef143
K. P. Wandinger, K. Wessel, P. Trillenberg, N. Heindl, H. Kirchner. (1998) Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients. Acta Neurologica Scandinavica 97:6, 359-365
CrossRef144
MARGARET FLYNN TAYLOR, DWIGHT D. WELLER, LESTER KOBZIK. (1998) Effect of TNF-α Antisense Oligomers on Cytokine Production by Primary Murine Alveolar Macrophages. Antisense and Nucleic Acid Drug Development 8:3, 199-205
CrossRef145
Abel Gayo, Lourdes Mozo, Ana Suárez, Alberto Tuñon, Carlos Lahoz, Carmen Gutiérrez. (1998) Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse. Journal of Neuroimmunology 85:2, 122-130
CrossRef146
P.A Calabresi, N.S Fields, E.C Farnon, J.A Frank, C.N Bash, T Kawanashi, H Maloni, S Jacobson, H.F McFarland. (1998) ELI-spot of Th-1 cytokine secreting PBMC's in multiple sclerosis: correlation with MRI lesions. Journal of Neuroimmunology 85:2, 212-219
CrossRef147
D. Matusevicius, P. Kivisakk, V. Navikas, W.-Z. Tian, M. Soderstrom, S. Fredrikson, H. Link. (1998) Influence of IFN-beta1b (Betaferon) on cytokine mRNA profiles in blood mononuclear cells and plasma levels of soluble VCAM-1 in multiple sclerosis. European Journal of Neurology 5:3, 265-275
CrossRef148
M Mycko, W Kowalski, M Kwinkowski, A.C Buenafe, B Szymanska, E Tronczynska, A Plucienniczak, K Selmaj. (1998) Multiple sclerosis: the frequency of allelic forms of tumor necrosis factor and lymphotoxin-alpha. Journal of Neuroimmunology 84:2, 198-206
CrossRef149
L.M Ossege, E Sindern, B Voss, J.-P Malin. (1998) Corticosteroids induce expression of transforming-growth-factor-beta1 mRNA in peripheral blood mononuclear cells of patients with multiple sclerosis. Journal of Neuroimmunology 84:1, 1-6
CrossRef150
Gianvito Martino, Fabio Grohovaz, Elena Brambilla, Franca Codazzi, Antonella Consiglio, Emilio Clementi, Massimo Filippi, Giancarlo Comi, Luigi M. E. Grimaldi. (1998) Proinflammatory cytokines regulate antigen-independent T-cell Activation by two separate calcium-signaling pathways in multiple sclerosis patients. Annals of Neurology 43:3, 340-349
CrossRef151
Dagan Schwartz, Dan Engelhard, Ruth Gallily, Israel Matoth, Talma Brenner. (1998) Glial cells production of inflammatory mediators induced by streptococcus pneumoniae: inhibition by pentoxifylline, low-molecular-weight heparin and dexamethasone. Journal of the Neurological Sciences 155:1, 13-22
CrossRef152
SIGRID R RUULS, JONATHON D SEDGWICK. (1998) Cytokine-directed therapies in multiple sclerosis and experimental autoimmune encephalomyelitis. Immunology and Cell Biology 76:1, 65-73
CrossRef153
Sampaio, Moraes, Nery, Santos, Matos, Sarno. (1998) Pentoxifylline decreases in vivo and in vitro tumour necrosis factor-alpha (TNF-alpha) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL). Clinical and Experimental Immunology 111:2, 300-308
CrossRef154
Armelle Ménard, Rim Amouri, Tomáš Dobránsky, Christiane Charriaut-Marlangue, Régine Pierig, Carmen Cifuentes-Diaz, Said Ghandour, James Belliveau, Hughes Gascan, Fayçal Hentati, Olivier Lyon-Caen, Hervé Perron, François Rieger. (1998) A gliotoxic factor and multiple sclerosis. Journal of the Neurological Sciences 154:2, 209-221
CrossRef155
Norbert Müller, Manfred Ackenheil. (1998) Psychoneuroimmunology and the cytokine action in the CNS: Implications for psychiatric disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry 22:1, 1-33
CrossRef156
Qingdi Li, Ron Milo, Hillel Panitch, Christopher T. Bever. (1998) Effect of Propranolol and IFN-β on the Induction of MHC Class II Expression and Cytokine Production by IFN-γ in THP-1 Human Monocytic Cells. Immunopharmacology and Immunotoxicology 20:1, 39-61
CrossRef157
Junliang Liu, Michael W. Marino, Grace Wong, Dianne Grail, Ashley Dunn, Jayaram Bettadapura, Anthony J. Slavin, Lloyd Old, Claude C.A. Bernard. (1998) TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination. Nature Medicine 4:1, 78-83
CrossRef158
Gianfranco Del Prete. (1998) The Concept of Type-1 and Type-2 Helper T Cells and Their Cytokines in Humans. International Reviews of Immunology 16:3-4, 427-455
CrossRef159
Philippe Monteyne, Valérie Van Laere, Roseline Marichal, Christian J.M Sindic. (1997) Cytokine mRNA expression in CSF and peripheral blood mononuclear cells in multiple sclerosis: detection by RT-PCR without in vitro stimulation. Journal of Neuroimmunology 80:1-2, 137-142
CrossRef160
M. Buttini, A. Mir, K. Appel, K. H. Wiederhold, S. Limonta, P. J. Gebicke-Haerter, H. W. G. M. Boddeke. (1997) Lipopolysaccharide induces expression of tumour necrosis factor alpha in rat brain: inhibition by methylprednisolone and by rolipram. British Journal of Pharmacology 122:7, 1483-1489
CrossRef161
Paola Sarchielli, Antonio Orlacchio, Federico Vicinanza, GianPiero Pelliccioli, Marinella Tognoloni, Carla Saccardi, Virgilio Gallai. (1997) Cytokine secretion and nitric oxide production by mononuclear cells of patients with multiple sclerosis. Journal of Neuroimmunology 80:1-2, 76-86
CrossRef162
Gianvito Martino, Antonella Consiglio, Diego M Franciotta, Angelo Corti, Massimo Filippi, Koen Vandenbroeck, Francesca L Sciacca, Giancarlo Comi, Luigi M.E. Grimaldi. (1997) Tumor necrosis factor α and its receptors in relapsing-remitting multiple sclerosis. Journal of the Neurological Sciences 152:1, 51-61
CrossRef163
William E. Hogancamp, Moses Rodriguez, Brian G. Weinshenker. (1997) Identification of Multiple Sclerosis-Associated Associated Genes. Mayo Clinic Proceedings 72:10, 965-976
CrossRef164
Denise M. Damek, Elizabeth A. Shuster. (1997) Pregnancy and Multiple Sclerosis. Mayo Clinic Proceedings 72:10, 977-989
CrossRef165
Jelena Drulović, Marija Mostarica-Stojković, Zvonimir Lević, Nebojša Stojsavljević, Vera Pravica, Šarlota Mesaroš. (1997) Interleukin-12 and tumor necrosis factor-α levels in cerebrospinal fluid of multiple sclerosis patients. Journal of the Neurological Sciences 147:2, 145-150
CrossRef166
C Pitzalis, B Sharrack, I.A Gray, A Lee, R.A.C Hughes. (1997) Comparison of the effects of oral versus intravenous methylprednisolone regimens on peripheral blood T lymphocyte adhesion molecule expression, T cell subsets distribution and TNF alpha concentrations in multiple sclerosis. Journal of Neuroimmunology 74:1-2, 62-68
CrossRef167
M Tateyama, I Nagano, M Yoshioka, K Chida, S Nakamura, Y Itoyama. (1997) Expression of tumor necrosis factor-α in muscles of polymyositis. Journal of the Neurological Sciences 146:1, 45-51
CrossRef168
Daniel A. Gamache, S. Dan Dimitrijevich, Lori K. Weimer, Laura S. Lang, Joan M. Spellman, Gustav Graff, John M. Yanni. (1997) Secretion of proinflammatory cytokines by human conjunctival epithelial cells. Ocular Immunology and Inflammation 5:2, 117-128
CrossRef169
Teruaki Iwahashi, Chang-Sung Koh, Atsushi Inoue, Nobuo Yanagisawa. (1997) Tumor Necrosis Factor-.ALPHA. and Transforming Growth Factor-.BETA. Production by Isolated Mononuclear Cells from the Spinal Cords of Lewis Rats with Experimental Autoimmune Encephalomyelitis.. The Tohoku Journal of Experimental Medicine 183:2, 123-133
CrossRef170
Anne H Cross, Richard M Keeling, Salil Goorha, Manuel San, Charles Rodi, Pamela S Wyatt, Pamela T Manning, Thomas P Misko. (1996) Inducible nitric oxide synthase gene expression and enzyme activity correlate with disease activity in murine experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 71:1-2, 145-153
CrossRef171
Dennis L. Kolson, Roger J. Pomerantz. (1996) AIDS dementia and HIV-1-induced neurotoxicity: Possible pathogenic associations and mechanisms. Journal of Biomedical Science 3:6, 389-414
CrossRef172
Richard A. Rudick, Richard M. Ransohoff, Richard Peppler, Sharon Vanderbrug Medendorp, Paul Lehmann, John Alam. (1996) Interferon beta induces interleukin-10 expression: Relevance to multiple sclerosis. Annals of Neurology 40:4, 618-627
CrossRef173
Bao-Guo Xiao, Guang-Xian Zhang, Cun-Gen Ma, Hans Link. (1996) The cerebrospinal fluid from patients with multiple sclerosis promotes neuronal and oligodendrocyte damage by delayed production of nitric oxide in vitro. Journal of the Neurological Sciences 142:1-2, 114-120
CrossRef174
N BRAUN, U MICHELL, B ERNST, R METZNER, A BITSCH, F WEBER, P RIECKMANN. (1996) Gene polymorphism at position ?308 of the tumor-necrosis -factor-? (TNF-?) in Multiple Sclerosis and it's influence on the regulation of TNF-? production. Neuroscience Letters 215:2, 75-78
CrossRef175
Antonio Garcia-Merino, Chester A. Alper, Koichiro Usuku, Deborah Marcus-Bagley, Robin Lincoln, Zuheir Awdeh, Edmond J. Yunis, George S. Eisenbarth, Stuart J. Brink, Stephen L. Hauser. (1996) Tumor Necrosis Pactor (TNF) microsatellite haplotypes in relation to extended haplotypes, susceptibility to diseases associated with the major histocompatibility complex and TNF secretion. Human Immunology 50:1, 11-21
CrossRef176
D.L. Madison, W.H. Kr
CrossRef177
S.V. Tan, R.J. Guiloff, D.C. Henderson, B.G. Gazzard, R. Miller. (1996) Aids-associated vacuolar myelopathy and tumor necrosis factor-alpha (TNFα). Journal of the Neurological Sciences 138:1-2, 134-144
CrossRef178
G. Birnbaum, L. Kotilinek, P. Schlievert, H.B. Clark, J. Trotter, E. Horvath, E. Gao, M. Cox, P.E. Braun. (1996) Heat shock proteins and experimental autoimmune encephalomyelitis (EAE): I. Immunization with a peptide of the myelin protein 2?,3? cyclic nucleotide 3? phosphodiesterase that is cross-reactive with a heat shock protein alters the course of EAE. Journal of Neuroscience Research 44:4, 381-396
CrossRef179
Simone Spuler (née Schönbeck), Tarek Yousry, Angela Scheller, Raymond Voltz, Ernst Holler, Matthias Hartmann, Manfred Wick, Reinhard Hohlfeld. (1996) Multiple sclerosis: prospective analysis of TNF-α and 55 kDa TNF receptor in CSF and serum in correlation with clinical and MRI activity. Journal of Neuroimmunology 66:1-2, 57-64
CrossRef180
D. Matusevicius, V. Navikas, M. Söderström, B.-G. Xiao, M. Haglund, S. Fredrikson, H. Link. (1996) Multiple sclerosis: the proinflammatory cytokines lymphotoxin-α and tumour necrosis factor-α are upregulated in cerebrospinal fluid mononuclear cells. Journal of Neuroimmunology 66:1-2, 115-123
CrossRef181
B.W. Van Oosten, M.H.G. Rep, R.A.W. Van Lier, P.E.T. Scholten, B.M.E. Von Blomberg, K.W. Pflughaupt, H.P. Hartung, H.J. Adér, C.H. Polman. (1996) A pilot study investigating the effects of orally administered pentoxifylline on selected immune variables in patients with multiple sclerosis. Journal of Neuroimmunology 66:1-2, 49-55
CrossRef182
M. Rentzos, C. Nikolaou, A. Rombos, K. Voumvourakis, I. Segditsa, C. Papageorgiou. (1996) Tumour necrosis factor alpha is elevated in serum and cerebrospinal fluid in multiple sclerosis and inflammatory neuropathies. Journal of Neurology 243:2, 165-170
CrossRef183
Ariel Miller, Naomi Lanir, Sarah Shapiro, Michel Revel, Silvia Honigman, Amalia Kinarty, Nitza Lahat. (1996) Immunoregulatory effects of interferon-β and interacting cytokines on human vascular endothelial cells implications for multiple sclerosis and other autoimmune diseases. Journal of Neuroimmunology 64:2, 151-161
CrossRef184
P.K. Coyle. (1996) The neuroimmunology of multiple sclerosis. Advances in Neuroimmunology 6:2, 143-154
CrossRef185
Yoshihiro Nishiura, Tatsufumi Nakamura, Katsuhiro Ichinose, Susumu Shirabe, Akira Tsujino, Hirofumi Goto, Takafumi Furuya, Shigenobu Nagataki. (1996) Increased Production of Inflammatory Cytokines in Cultured CD4+ Cells from Patients with HTLV-I-Associated Myelopathy.. The Tohoku Journal of Experimental Medicine 179:4, 227-233
CrossRef186
Roland Martin, Henry McFarland. (1996) Experimental immunotherapies for multiple sclerosis. Springer Seminars in Immunopathology 18:1, 1-24
CrossRef187
Marco Rovaris, David Barnes, Nicola Woodrofe, George H. du Boulay, John W. Thorpe, Alan J. Thompson, W. Ian McDonald, David H. Miller. (1996) Patterns of disease activity in multiple sclerosis patients: A study with quantitative gadolinium-enhanced brain MRI and cytokine measurement in different clinical subgroups. Journal of Neurology 243:7, 536-542
CrossRef188
Bing He, Vaidrius Navikas, Joakim Lundahl, Mats Söderström, Jan Hillert. (1995) Tumor necrosis factor α-308 alleles in multiple sclerosis and optic neuritis. Journal of Neuroimmunology 63:2, 143-147
CrossRef189
Gary A. Rosenberg, Edward Y. Estrada, John E. Dencoff, William G. Stetler-Stevenson. (1995) Tumor necrosis factor-α-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window. Brain Research 703:1-2, 151-155
CrossRef190
Frauke Zipp, Frank Weber, Susanne Huber, Stefano Sotgiu, Anna Czlonkowska, Ernst Holler, Ekkehard Albert, Elisabeth H. Weiss, Hartmut Wekerle, Reinhard Hohlfeld. (1995) Genetic control of multiple sclerosis: Increased production of lymphotoxin and tumor necrosis factor-? by HLA-DR2+ T cells. Annals of Neurology 38:5, 723-730
CrossRef191
Bruce F. Bebo, D.Scott Linthicum. (1995) Expression of mRNA for 55-kDa and 75-kDa tumor necrosis factor (TNF) receptors in mouse cerebrovascular endothelium: effects of interleukin-1β, Interferon-γ and TNF-α on cultured cells. Journal of Neuroimmunology 62:2, 161-167
CrossRef192
Erwin G. Van Meir. (1995) Cytokines and tumors of the central nervous system. Glia 15:3, 264-288
CrossRef193
J. N. Whitaker, R. D. Kachelhofer, E. L. Bradley, S. Burgard, B. A. Layton, A. T. Reder, W. Morrison, G. J. Zhao, D. W. Paty. (1995) Urinary myelin basic protein?like material as a correlate of the progression of multiple sclerosis. Annals of Neurology 38:4, 625-632
CrossRef194
M. A. Deli, L. Descamps, M.-P. Dehouck, R. Cecchelli, F. Jo
CrossRef195
Hans-Peter Hartung, Karlheinz Reiners, Juan J. Archelos, Marco Michels, Pierrette Seeldrayers, Fedor Heidenreich, Karl W. Pflughaupt, Klaus V. Toyka. (1995) Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: Correlation with magnetic resonance imaging. Annals of Neurology 38:2, 186-193
CrossRef196
Karl Roessler, Gerda Suchanek, Helene Breitschopf, Klaus Kitz, Christian Matula, Hans Lassmann, Wolfgang Th. Koos. (1995) Detection of tumor necrosis factor-α protein and messenger RNA in human glial brain tumors: comparison of immunohistochemistry with in situ hybridization using molecular probes. Journal of Neurosurgery 83:2, 291-297
CrossRef197
J.M. Keppel Hesselink. (1995) The role of tumour necrosis factor α in the pathogenesis of multiple sclerosis, and pentoxifylline as a possible pharmacotherapeutic intervention. European Journal of Neurology 2:3, 177-180
CrossRef198
Nancy B. Beamer, Bruce M. Coull, Wayne M. Clark, J. Samantha Hazel, Jenny R. Silberger. (1995) Interleukin-6 and interleukin-1 receptor antagonist in acute stroke. Annals of Neurology 37:6, 800-805
CrossRef199
B. Soliven, S. Szuchet. (1995) Signal transduction pathways in oligodendrocytes: Role of tumor necrosis factor-α. International Journal of Developmental Neuroscience 13:3-4, 351-367
CrossRef200
Etty N. Benveniste, Li Ping Tang, Robert M. Law. (1995) Differential regulation of astrocyte TNF-α expression by the cytokines TGF-β, IL-6 and IL-10. International Journal of Developmental Neuroscience 13:3-4, 341-349
CrossRef201
Shalini Bansil, Stuart D. Cook, Christine Rohowsky-Kochan. (1995) Multiple sclerosis: Immune mechanism and update on current therapies. Annals of Neurology 37:S1, 87-101
CrossRef202
TOMAS OLSSON. (1995) Critical Influences of the Cytokine Orchestration on the Outcome of Myelin Antigen-Specific T-Cell Autoimmunity in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. Immunological Reviews 144:1, 245-268
CrossRef203
Ryuji Miyagishi, Seiji Kikuchi, Toshiyuki Fukazawa, Kunio Tashiro. (1995) Macrophage inflammatory protein-1α in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases. Journal of the Neurological Sciences 129:2, 223-227
CrossRef204
A. Glabinski, M. Mirecka, L. Pokoca. (1995) Tumor necrosis factor alpha but not lymphotoxin is overproduced by blood mononuclear cells in multiple sclerosis.. Acta Neurologica Scandinavica 91:4, 276-279
CrossRef205
Cedric S. Raine. (1995) Multiple sclerosis: TNF revisited, with promise. Nature Medicine 1:3, 211-214
CrossRef206
David Martin, Stephanie L. Near, Alison Bendele, Deborah A. Russell. (1995) Inhibition of tumor necrosis factor is protective against neurologic dysfunction after active immunization of lewis rats with myelin basic protein. Experimental Neurology 131:2, 221-228
CrossRef207
P. Rieckmann, M. Albrecht, B. Kitze, T. Weber, H. Tumani, A. Broocks, W. L
CrossRef208
C. E. Shaw, P. R. Dunbar, H. A. Macaulay, T. J. Neale. (1995) Measurement of immune markers in the serum and cerebrospinal fluid of multiple sclerosis patients during clinical remission. Journal of Neurology 242:2, 53-58
CrossRef209
T. Tsukamoto, M. Ishikawa, T. Yamamoto. (1995) Suppressive effects of TNF-α on myelin formation in vitro. Acta Neurologica Scandinavica 91:1, 71-75
CrossRef210
T. Olsson. (1994) Role of cytokines in multiple sclerosis and experimental autoimmune encephalomyelitis. European Journal of Neurology 1:1, 7-19
CrossRef211
Johan T.M. Frieling, Robert W. Sauerwein, John Wijdenes, Thijs Hendriks, Cees J. van der Linden. (1994) Soluble interleukin 6 receptor in biological fluids from human origin. Cytokine 6:4, 376-381
CrossRef212
D.M. Barten, N.H. Ruddle. (1994) Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis. Journal of Neuroimmunology 51:2, 123-133
CrossRef213
Marie-Paule Roth, Leonor Nogueira, Hélène Coppin, Michel Clanet, John Clayton, Anne Cambon-Thomsen. (1994) Tumor necrosis factor polymorphisms in multiple sclerosis: No additional association independent of HLA. Journal of Neuroimmunology 51:1, 93-99
CrossRef214
Jack P. Antel, Kenneth Williams, Manon Blain, Ellie McRea, JoAnne McLaurin. (1994) Oligodendrocyte lysis by CD4+ T cells independent of tumor necrosis factor. Annals of Neurology 35:3, 341-348
CrossRef215
Dan Lehmann, Dimitrios Karussis, Rachel Misrachi-Koll, Eli Shezen, Haim Ovadia, Oded Abramsky. (1994) Oral administration of the oxidant-scavenger N-acetyl-l-cysteine inhibits acute experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 50:1, 35-42
CrossRef216
Toufic Renno, Jia-You Lin, Ciriaco Piccirillo, Jack Antel, Trevor Owens. (1994) Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice. Journal of Neuroimmunology 49:1-2, 1-7
CrossRef217
Alastair Compston. (1994) Future prospects for the management of multiple sclerosis. Annals of Neurology 36:S1, S146-S150
CrossRef218
M.N. Woodroofe, M.L. Cuzner. (1993) Cytokine mRNA expression in inflammatory multiple sclerosis lesions: Detection by non-radioactive in situ hybridization. Cytokine 5:6, 583-588
CrossRef219
Jongbum Kwon, Yup Chung, Etty N. Benveniste. (1993) Cloning and sequence analysis of the rat tumor necrosis factor-encoding genes. Gene 132:2, 227-236
CrossRef220
Paolo Confalonieri, Carlo Antozzi, Ferdinando Cornelio, Ornella Simoncini, Renato Mantegazza. (1993) Immune activation in myasthenia gravis: Soluble interleukin-2 receptor, interferon-γ and tumor necrosis factor-α levels in patients' serum. Journal of Neuroimmunology 48:1, 33-36
CrossRef221
M. Huberman, F. Shalit, I. Roth-Deri, B. Gutman, E. Kott, B. Sredni. (1993) Decreased IL-3 production by peripheral blood mononuclear cells in patients with multiple sclerosis. Journal of the Neurological Sciences 118:1, 79-82
CrossRef222
Hillel S. Panitch, Christopher T. Bever. (1993) Clinical trials of interferons in multiple sclerosis what have we learned?. Journal of Neuroimmunology 46:1-2, 155-164
CrossRef223
M. K. Sharief, B. McLean, E. J. Thompson. (1993) Elevated serum levels of tumor necrosis factor-? in Guillain-Barr
CrossRef224
Guido Stoll, Stefan Jung, Sebastian Jander, Peter van der Meide, Hans-Peter Hartung. (1993) Tumor necrosis factor-α in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system. Journal of Neuroimmunology 45:1-2, 175-182
CrossRef225
Hans-Peter Hartung. (1993) Immune-mediated demyelination. Annals of Neurology 33:6, 563-567
CrossRef226
Flier, Jeffrey S., Underhill, Lisa H., Hollsberg, PerHafler, David A.. (1993) Pathogenesis of Diseases Induced by Human Lymphotropic Virus Type I Infection. New England Journal of Medicine 328:16, 1173-1182
Full Text227
Talma Brenner, Aviva Yamin, Oded Abramsky, Ruth Gallily. (1993) Stimulation of tumor necrosis factor-α production by mycoplasmas and inhibition by dexamethasone in cultured astrocytes. Brain Research 608:2, 273-279
CrossRef228
Peter Zabel, F. Ulrich Schade, Max Schlaak. (1993) Inhibition of endogenous TNF formation by pentoxifylline. Immunobiology 187:3-5, 447-463
CrossRef229
M.K. Sharief, M.A. Noori, M. Ciardi, A. Cirelli, E.J. Thompson. (1993) Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis. Correlation with TNF-α and blood-brain barrier damage. Journal of Neuroimmunology 43:1-2, 15-21
CrossRef230
R.M. McCarron, L. Wang, M.K. Racke, D.E. McFarlin, M. Spatz. (1993) Cytokine-regulated adhesion between encephalitogenic T lymphocytes and cerebrovascular endothelial cells. Journal of Neuroimmunology 43:1-2, 23-30
CrossRef231
Rhonda R. Voskuhl, Roland Martin, Cheryl Bergman, Mira Dalal, Nancy H. Ruddle, Henry F. Mcfarland. (1993) T Helper 1 (TH1) Functional Phenotype of Human Myelin Basic Protein-Specific T Lymphocytes. Autoimmunity 15:2, 137-143
CrossRef232
P MEGYERI, C ABRAHAM, P TEMESVARI, J KOVACS, T VAS, C SPEER. (1992) Recombinant human tumor necrosis factor α constricts pial arterioles and increases blood-brain barrier permeability in newborn piglets. Neuroscience Letters 148:1-2, 137-140
CrossRef233
Fionula M. Brennan, Marc Feldmann. (1992) Cytokines in autoimmunity. Current Opinion in Immunology 4:6, 754-759
CrossRef234
W.R. Lamb, R.S.H. Pumphrey, P.E.C. Brenchley. (1992) A peroxidase-linked enzyme immunoassay for tumour necrosis factor α utilising alternative colorimetric or chemilumimetric substrates. Journal of Immunological Methods 155:2, 215-223
CrossRef235
M. Deckert-Schlüter, D. Schlüter, G. Schwendemann. (1992) Evaluation of IL-2, sIL2R, IL-6, TNF-α, and IL-1β levels in serum and CSF of patients with optic neuritis. Journal of the Neurological Sciences 113:1, 50-54
CrossRef236
Hans-Peter Hartung, Stefan Jung, Guido Stoll, Jürgen Zielasek, Beate Schmidt, Juan J. Archelos, Klaus V. Toyka. (1992) Inflammatory mediators in demyelinating disorders of the CNS and PNS. Journal of Neuroimmunology 40:2-3, 197-210
CrossRef237
Rogier Q. Hintzen, Chris H. Polman, Cees J. Lucas, RenéA.W. van Lier. (1992) Multiple sclerosis: immunological findings and possible implications for therapy. Journal of Neuroimmunology 39:1-2, 1-10
CrossRef238
L. M. E. Grimaldi, G. V. Martino, D. M. Franciotta, R. Brustia, A. Castagna, R. Prister
CrossRef239
M.K. Sharief, E.J. Thompson. (1992) In vivo relationship of tumor necrosis factor-α to blood-brain barrier damage in patients with active multiple sclerosis. Journal of Neuroimmunology 38:1-2, 27-33
CrossRef240
Richard M. Ransohoff, Vincent K. Tuohy, Barbara P. Barna, Richard A. Rudick. (1992) Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vitro despite decreased HLA-DR density in vivo. Journal of Neuroimmunology 37:3, 169-176
CrossRef241
Barry G.W. Arnason. (1992) Multiple sclerosis: additional thoughts. Journal of the Neurological Sciences 107:2, 141-144
CrossRef242
(1992) Tumor Necrosis Factor-α and Disease Progression in Multiple Sclerosis. New England Journal of Medicine 326:4, 272-273
Full Text243
Jingwu Zhang, Howard L. Weiner, David A. Hafler. (1992) Autoreactive T Cells in Multiple Sclerosis. International Reviews of Immunology 9:3, 183-201
CrossRef244
Hartmut Wekerle. (1991) Neurological diseases. Current Opinion in Immunology 3:6, 896-901
CrossRef
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