Interleukin-10 and Graft-versus-Host Disease
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《新英格兰医药杂志》
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
References
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.
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.
Deeg HJ. Cytokines in graft-versus-host disease and the graft-versus-leukemia reaction. Int J Hematol 2001;74:26-32.
The authors reply: 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
References
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.
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.
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.
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.
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.
Yujiro Kida, M.D., Ph.D.
Tokyo Metropolitan Komagome Hospital
Tokyo 113-8677, Japan
References
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.
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.
Deeg HJ. Cytokines in graft-versus-host disease and the graft-versus-leukemia reaction. Int J Hematol 2001;74:26-32.
The authors reply: 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
References
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.
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.
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.
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.
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.