Correspondence

Interleukin-10 and Graft-versus-Host Disease

N Engl J Med 2004; 350:1361-1362March 25, 2004

Article

To the Editor:

Lin et al. (Dec. 4 issue)1 conclude that recipients of allogeneic bone marrow who have the interleukin-10 (IL10) –592A/A genotype have a lower risk of severe acute graft-versus-host disease (GVHD) than recipients who have the –592C/C genotype. The authors hypothesize that a high level of interleukin-10 production is associated with the –592A/A genotype and mitigates the intensity of GVHD-induced inflammation. However, Lin et al. did not measure serum interleukin-10 levels in the recipients they studied. Miura et al. have reported that patients with the IL10 –592A/C genotype or –592A/A genotype have reduced levels of IL10 messenger RNA (mRNA) transcripts in their peripheral-blood mononuclear cells and a reduced incidence of GVHD.2 Miura et al. have also reported that the level of cytokine production is directly related to the level of mRNA expression. Interleukin-10 may have both immunostimulatory and immunoregulatory effects, leading to either GVHD-related deterioration or amelioration of this post-transplantation complication.3 Therefore, it is unclear whether the recipients with the IL10 –592A/A genotype have high levels of interleukin-10 production and whether high levels of interleukin-10 decrease the risk of severe GVHD.

Yujiro Kida, M.D., Ph.D.
Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677, Japan

3 References

1. 1

   Lin M-T, Storer B, Martin PJ, et al. Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med 2003;349:2201-2210
   Full Text | Web of Science | Medline

2. 2

   Miura Y, Thoburn CJ, Bright EC, Chen W, Nakao S, Hess AD. Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD): interleukin 10 and interferon gamma may be critical mediators for the development of autologous GVHD. Blood 2002;100:2650-2658
   CrossRef | Web of Science | Medline

3. 3

   Deeg HJ. Cytokines in graft-versus-host disease and the graft-versus-leukemia reaction. Int J Hematol 2001;74:26-32
   CrossRef | Web of Science | Medline

Author/Editor Response

The association between IL10 promoter genotypes and the risk of GVHD in our study was similar to the finding reported by Miura et al.,1 but our interpretations differ. High interleukin-10 production by ex vivo stimulated recipient cells before allogeneic hematopoietic-cell transplantation has been associated with reduced risks of GVHD and early death.2,3 However, high serum interleukin-10 levels after transplantation have been associated with an increased risk of GVHD and a fatal outcome.4,5 High serum interleukin-10 levels in patients with severe GVHD could represent a late compensatory response that correlates with the severity of GVHD, as suggested by the data reported by Miura et al.1 The interleukin-10 response may be dynamic and may vary among patients at different times before and after transplantation. We agree that further studies are needed to clarify the genetic control of interleukin-10 production and the role of interleukin-10 in hematopoietic-cell transplantation.

Ming-Tseh Lin, M.D., Ph.D.
Paul J. Martin, M.D.
John A. Hansen, M.D.
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024
jhansen@fhcrc.org

5 References

1. 1

   Miura Y, Thoburn CJ, Bright EC, Chen W, Nakao S, Hess AD. Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD): interleukin 10 and interferon gamma may be critical mediators for the development of autologous GVHD. Blood 2002;100:2650-2658
   CrossRef | Web of Science | Medline

2. 2

   Baker KS, Roncarolo MG, Peters C, Bigler M, DeFor T, Blazar BR. High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths. Bone Marrow Transplant 1999;23:1123-1129
   CrossRef | Web of Science | Medline

3. 3

   Holler E, Roncarolo MG, Hintermeier-Knabe R, et al. Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation. Bone Marrow Transplant 2000;25:237-241
   CrossRef | Web of Science | Medline

4. 4

   Hempel L, Korholz D, Nussbaum P, Bonig H, Burdach S, Zintl F. High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation. Bone Marrow Transplant 1997;20:365-368
   CrossRef | Web of Science | Medline

5. 5

   Takatsuka H, Takemoto Y, Okamoto T, et al. Predicting the severity of graft-versus-host disease from interleukin-10 levels after bone marrow transplantation. Bone Marrow Transplant 1999;24:1005-1007
   CrossRef | Web of Science | Medline

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