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Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-08-2566. This Article Full Text (PDF) All Versions of this Article: 2002-08-2566v1 101/7/2877    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 Reddy, P. Articles by Ferrara, J. L M Search for Related Content PubMed PubMed Citation Articles by Reddy, P. Articles by Ferrara, J. L M Social Bookmarking                   What's this? Submitted August 20, 2002 Accepted October 30, 2002 Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects Pavan Reddy, Takanori Teshima, Gerhard Hildebrandt, Debra L Williams, Chen Liu, Kenneth R Cooke, and James L M Ferrara* Department of Internal Medicine and Pediatrics, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA * Corresponding author; email: ferrara{at}umich.edu. Interleukin 18 is a unique cytokine that modulates both Th1/Th2 responses but its ability to modulate diseases through induction of Th2 cytokines is unclear. Because immune responses of allogeneic bone marrow donors may affect acute graft versus host disease (GVHD), we investigated the effect of pretreating bone marrow transplant (BMT) donors with IL-18 on the severity of acute GVHD using a well-characterized experimental BMT model (BALB/cB6). Pretreatment of allogeneic BMT donors with IL-18 significantly improved survival (80% vs 0%, P < 0.001), and reduced clinical, biochemical and pathologic indices of acute GVHD in BMT recipients. IL-18 pretreatment was associated with reduced IFN-and greater IL-4 secretion by donor T cells after BMT. Acute GVHD mortality was reduced when IL-18 was administered to donors deficient in and STAT4 and IFN-but not STAT6 signaling molecules, confirming the role of STAT6 signaling in IL-18's protective effect. IL-18 treatment did not alter donor CD8+ cytotoxic T lymphocyte (CTL) activity and preserved graft versus leukemia (GVL) effects after allogeneic BMT (70% v 10%, P < 0.01). Together, these data illustrate that pretreatment of donors with IL-18 prior to allogeneic BMT attenuates acute GVHD in a STAT6 dependent mechanism while preserving GVL effects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [Abstract] [Full Text] [PDF] J. H. Kim, E. Y. Choi, and D. H. Chung Donor Bone Marrow Type II (Non-V{alpha}14J{alpha}18 CD1d-Restricted) NKT Cells Suppress Graft-Versus-Host Disease by Producing IFN-{gamma} and IL-4 J. Immunol., November 15, 2007; 179(10): 6579 - 6587. [Abstract] [Full Text] [PDF] E. S. Morris, K. P. A. MacDonald, and G. R. Hill Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? Blood, May 1, 2006; 107(9): 3430 - 3435. [Abstract] [Full Text] [PDF] B. R Blazar and W. J Murphy Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD) Phil Trans R Soc B, September 29, 2005; 360(1461): 1747 - 1767. [Abstract] [Full Text] [PDF] D. Hashimoto, S. Asakura, S. Miyake, T. Yamamura, L. Van Kaer, C. Liu, M. Tanimoto, and T. Teshima Stimulation of Host NKT Cells by Synthetic Glycolipid Regulates Acute Graft-versus-Host Disease by Inducing Th2 Polarization of Donor T Cells J. Immunol., January 1, 2005; 174(1): 551 - 556. [Abstract] [Full Text] [PDF] P. Reddy, Y. Maeda, K. Hotary, C. Liu, L. L. Reznikov, C. A. Dinarello, and J. L. M. Ferrara Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect PNAS, March 16, 2004; 101(11): 3921 - 3926. [Abstract] [Full Text] [PDF]

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