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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0176. This Article Full Text (PDF) All Versions of this Article: 2002-01-0176v1 100/7/2650    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Miura, Y. Articles by Hess, A. D Search for Related Content PubMed PubMed Citation Articles by Miura, Y. Articles by Hess, A. D Social Bookmarking                   What's this? Submitted January 28, 2002 Accepted May 27, 2002 Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD): interleukin-10 and interferon- may be critical mediators for the development of autologous GVHD Yuji Miura, Christopher J Thoburn, Emilie C Bright, Weiran Chen, Shinji Nakao, and Allan D Hess* Oncology Center, Johns Hopkins University, Baltimore, MD, USA Cellular Transplantion Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan * Corresponding author; email: adhess{at}jhmi.edu. Administration of the immunosuppressive drug cyclosporine A (CsA) following autologous stem cell transplantation paradoxically elicits a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with autoreactive CD8+ T cells that recognize MHC class II determinants in association with a peptide from the invariant chain. To investigate the potential role of cytokines and chemokines in autologous GVHD, interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-, and macrophage inflammatory protein-1 (MIP-1) gene expression in peripheral blood mononuclear cells (PBMCs) was determined in 36 patients treated with CsA following transplantation and correlated with the induction of cytolytic activity against autologous phytohemagglutinin-stimulated lymphocytes (PHA-blasts) and the breast cancer cell line (T47D). The determination of gene expression by real-time PCR revealed that IL-10 mRNA levels by PBMCs in patients with autologous GVHD were 29-fold higher than in normal individuals. IFN- (4-fold), IL-2 (3-fold) and MIP-1 (44-fold) mRNA levels were also increased in GVHD-induced patients compared to normal individuals. The ability of PBMCs to lyse autologous PHA-blasts and T47D tumor cells exhibited an identical temporal relationship with expression of IL-10 and IFN- during autologous GVHD. Moreover, the susceptibility to autologous GVHD as assessed in 75 patients was significantly associated with the IL-10-1082 G/G polymorphic alleles, allelic variants in the promoter region that govern IL-10 production. These findings indicate that IL-10 may play an unexpected but critical role in autologous GVHD and could be utilized to enhance a graft-versus-tumor effect posttransplant. Interestingly, polymorphisms in the IL-10 promoter region may also explain differences in the susceptibility of patients for autologous GVHD induction. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. G. Berdeja, A. Hess, D. M. Lucas, P. O'Donnell, R. F. Ambinder, L. F. Diehl, D. Carter-Brookins, S. Newton, and I. W. 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