Correspondence
Inflammatory Bowel Disease
N Engl J Med 2002; 347:1982-1984December 12, 2002
- Article
To the Editor:
In his review of inflammatory bowel disease (Aug. 8 issue),1 Podolsky refers to interleukin-10 as a down-regulatory cytokine, citing findings in murine models. However, recent data do not support an antiinflammatory role for interleukin-10 in patients with inflammatory bowel disease. In this regard, Tilg et al. reported that recombinant interleukin-10 administered to patients with Crohn's disease increased the production of interferon-γ.2 The inflammatory role of interleukin-10 found in their study paralleled the absence of significant benefits in clinical trials assessing the efficacy of high doses of recombinant human interleukin-10.3,4 Such data reveal the complexity of the cytokine network in human inflammatory bowel disease, as well as the need for applying the findings of basic research to clinical practice cautiously.
4 ReferencesJaime García de Tena, M.D., Ph.D.
Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Spain
jgtena@terra.es Luis Manzano Espinosa, M.D., Ph.D.
Hospital Universitario Ramón Cajal, 28034 Madrid, SpainMelchor Alvarez-Mon, M.D., Ph.D.
Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Spain1
Podolsky DK . Inflammatory bowel disease. N Engl J Med 2002;347:417-429
Full Text | Web of Science | Medline2
Tilg H ,van Montfrans C ,van den Ende A , et al. Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma. Gut 2002;50:191-195
CrossRef | Web of Science | Medline3
Schreiber S ,Fedorak RN ,Nielsen OH , et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Gastroenterology 2000;119:1461-1472
CrossRef | Web of Science | Medline4
Fedorak RN ,Gangl A ,Elson CO , et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. Gastroenterology 2000;119:1473-1482
CrossRef | Web of Science | Medline
To the Editor:
Podolsky states that probiotics may have a role in the treatment of inflammatory bowel disease. However, probiotics include many different preparations that are not equivalent in terms of efficacy. For example, available probiotics may contain bacteria at low, intermediate, or high concentrations (106 to 108, 109 to 1010, or 1011 or more colony-forming units per gram, respectively). Some preparations are made with only one bacterial strain; others, with two or more strains. Clinical studies of the use of probiotics with lactobacillus have shown variable results.1-4 Thus, medical articles that refer to probiotics in a nonspecific manner may be misleading.
4 ReferencesGiuseppe Famularo, M.D., Ph.D.
San Camillo Hospital, 00152 Rome, Italy
gfamularo@uni.net Vito Trinchieri, M.D.
Claudio De Simone, M.D.
University of L'Aquila, 67100 L'Aquila, Italy1
Venturi A ,Gionchetti P ,Rizzello F , et al. Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999;13:1103-1108
CrossRef | Web of Science | Medline2
Gionchetti P ,Rizzello F ,Venturi A , et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000;119:305-309
CrossRef | Web of Science | Medline3
Ulisse S ,Gionchetti P ,D'Alo S , et al. Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis: effects of probiotic treatment. Am J Gastroenterol 2001;96:2691-2699
CrossRef | Web of Science | Medline4
Prantera C ,Scribano ML ,Falasco G ,Andreoli A ,Luzi C . Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG. Gut 2002;51:405-409
CrossRef | Web of Science | Medline
To the Editor:
In presenting various therapeutic options for the management of Crohn's disease, Podolsky briefly considers elemental nutrition, stressing the limited compliance with this approach. However, as discussed in a review by Ruemmele et al.,1 such a nutritional approach can induce clinical remission and improve the growth failure associated with childhood Crohn's disease.1,2 Moreover, a majority of young patients with growth failure are strongly motivated to accept tube feeding. The acceptance of this approach has increased with new oral formulas.1
Administration of thalidomide to patients with refractory Crohn's disease represents another important therapeutic option that is not emphasized in Podolsky's review. In our experience,3 a low dose of thalidomide (0.5 to 2 mg per kilogram of body weight per day) was effective in inducing a sustained remission (two to five years) in patients with severe, refractory, corticosteroid-dependent Crohn's disease.
3 ReferencesFederico Marchetti, M.D.
Stefano Martelossi, M.D.
Alessandro Ventura, M.D.
Università di Trieste, 34100 Trieste, Italy
marchetti@burlo.trieste. it 1
Ruemmele FM ,Roy CC ,Levy E ,Seidman EG . Nutrition as primary therapy in pediatric Crohn's disease: fact or fantasy? J Pediatr 2000;136:285-291
CrossRef | Web of Science | Medline2
Belli D ,Seidman EG ,Bouthillier L , et al. Chronic intermittent elemental diet improves growth failure in children with Crohn's disease. Gastroenterology 1988;94:603-610
Web of Science | Medline3
Facchini S ,Candusso M ,Martelossi S ,Liubich M ,Panfili E ,Ventura A . Efficacy of long-term treatment with thalidomide in children and young adults with Crohn disease: preliminary results. J Pediatr Gastroenterol Nutr 2001;32:178-181
CrossRef | Web of Science | Medline
To the Editor:
In his extensive review of inflammatory bowel disease, Podolsky states that “surgery can have an important role in management, though a full consideration is beyond the scope of this review.” This statement strikes me as inadequate and uninformative. It gives the reader the impression that surgical management is completely separate from medical management, which should not be so. Joint management based on both disciplines is the key to success in the care of patients with complicated disease.
Podolsky's discussion of the use of antibiotics is also incomplete. Metronidazole is an agent that should be considered for the prevention of postoperative relapse. In a randomized, controlled trial, metronidazole at a dose of 20 mg per kilogram of body weight given daily for three months after ileal resection significantly reduced the rate of endoscopic recurrence, to 52 percent as compared with 75 percent in the placebo group.1 Further studies are required to confirm the benefit of longer-term treatment. Another trial2 showed the efficacy of ornidazole at a dose of 1 g per day. This nitroimidazol antibiotic decreased the rate of endoscopic recurrence and also significantly diminished the rate of clinical recurrence.
2 ReferencesFaiyaz Mohammed, M.R.C.P.
Royal Oldham Hospital, Oldham OL1 2JH, United Kingdom
safai@hotmail.com 1
Rutgeerts P ,Hiele M ,Geboes K , et al. Controlled trial of metronidazole treatment for prevention of Crohn's disease after ileal resection. Gastroenterology 1995;108:1617-1621
CrossRef | Web of Science | Medline2
Rutgeerts PJ ,D'Haens G ,Baert F , et al. Nitroimidazol antibiotics are efficacious for prophylaxis of postoperative recurrence of Crohn's disease: a placebo controlled trial. Gastroenterology 1999;116:A808-A808 abstract.
Web of Science
Author/Editor Response
Dr. Podolsky replies:
To the Editor: In my review, I endeavored to highlight current concepts of the pathogenesis and approaches to treatment of inflammatory bowel diseases within the limited space available, with the intention that the article serve the needs of the general readership of the Journal. Therefore, in reply to Mohammed: space limitations did not permit a discussion of surgery, although the coordinated use of medical and surgical approaches is axiomatic for many clinical problems and not unique to inflammatory bowel disease. Although the data on the effect of metronidazole given for postoperative prophylaxis are interesting, the trial periods fall well short of the length needed to judge its value in routine care, and few would accept that its efficacy in this setting is proven.
Marchetti and colleagues are correct in noting that nutritional therapy may be more acceptable to children than to adults and accordingly that such therapy may have a more important role in younger age groups. I disagree that thalidomide represents an important option. Although, as noted in the article, two pilot studies have suggested efficacy, the effects are modest. Larger, well-controlled trials of thalidomide in selected groups of patients over longer periods would be welcome. Famularo and colleagues are probably correct in suggesting that the efficacy of probiotics may depend on the composition of the agent being administered as well as other variables, including the type and location of disease, although the available data remain limited.
Finally, García de Tena et al. are correct in noting that the efficacy of interleukin-10 observed in clinical trials to date has been limited, if present at all. It is possible that better results may be obtained with the use of creative approaches currently being developed, in which greater local concentrations of this down-regulatory cytokine can be delivered. These approaches include both the use of engineered probiotic bacteria that can express interleukin-10 in the lumen of the gut and gene therapy.
Daniel K. Podolsky, M.D.
Massachusetts General Hospital, Boston, MA 02114- Citing Articles (4)
Citing Articles
1
Antonio Tursi, Giovanni Brandimarte, Alfredo Papa, Andrea Giglio, Walter Elisei, Gian Marco Giorgetti, Giacomo Forti, Sergio Morini, Cesare Hassan, Maria Antonietta Pistoia, Maria Ester Modeo, Stefano Rodino', Teresa D'Amico, Ladislava Sebkova, Natale Sacca', Emilio Di Giulio, Francesco Luzza, Maria Imeneo, Tiziana Larussa, Salvatore Di Rosa, Vito Annese, Silvio Danese, Antonio Gasbarrini. (2010) Treatment of Relapsing Mild-to-Moderate Ulcerative Colitis With the Probiotic VSL#3 as Adjunctive to a Standard Pharmaceutical Treatment: A Double-Blind, Randomized, Placebo-Controlled Study. The American Journal of Gastroenterology 105:10, 2218-2227
CrossRef2
Jaime García De Tena, Luis Manzano, Juan Carlos Leal, Esther San Antonio, Verónica Sualdea, Melchor Álvarez-Mon. (2006) Distinctive Pattern of Cytokine Production and Adhesion Molecule Expression in Peripheral Blood Memory CD4+ T Cells from Patients with Active Crohn’s Disease. Journal of Clinical Immunology 26:3, 233-242
CrossRef3
Michael Schultz, Claudia G??ttl, Rose J. Young, Peter Iwen, Jon A. Vanderhoof. (2004) Administration of Oral Probiotic Bacteria to Pregnant Women Causes Temporary Infantile Colonization. Journal of Pediatric Gastroenterology and Nutrition 38:3, 293-297
CrossRef4
J. García de Tena, L. Manzano Espinosa, J.C. Leal Berral, M. Álvarez-Mon Soto. (2004) Etiopatogenia de la enfermedad inflamatoria del tubo digestivo. Medicine - Programa de Formación Médica Continuada Acreditado 9:5, 331-340
CrossRef
