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Interleukin-18 Regulates Acute Graft-Versus-Host Disease by Enhancing Fas-mediated Donor T Cell Apoptosis
| Content Provider | Semantic Scholar |
|---|---|
| Author | Reddy, Pavan Teshima, Takanori Kukuruga, Mark Ordemann, Rainer Liu, Chen Lowler, Kathy |
| Copyright Year | 2001 |
| Abstract | Interleukin (IL)-18 is a recently discovered cytokine that modulates both T helper type 1 (Th1) and Th2 responses. IL-18 is elevated during acute graft-versus-host disease (GVHD). We investigated the role of IL-18 in this disorder using a well characterized murine bone marrow transplantation (BMT) model (B6 --> B6D2F1). Surprisingly, blockade of IL-18 accelerated acute GVHD-related mortality. In contrast, administration of IL-18 reduced serum tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS) levels, decreased intestinal histopathology, and resulted in significantly improved survival (75 vs. 15%, P < 0.001). Administration of IL-18 attenuated early donor T cell expansion and was associated with increased Fas expression and greater apoptosis of donor T cells. The administration of IL-18 no longer protected BMT recipients from GVHD when Fas deficient (lpr) mice were used as donors. IL-18 also lost its ability to protect against acute GVHD when interferon (IFN)-gamma knockout mice were used as donors. Together, these results demonstrate that IL-18 regulates acute GVHD by inducing enhanced Fas-mediated apoptosis of donor T cells early after BMT, and donor IFN-gamma is critical for this protective effect. |
| Starting Page | 1433 |
| Ending Page | 1440 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 11714750 |
| Volume Number | 194 |
| Journal | The Journal of experimental medicine |
| Alternate Webpage(s) | http://jem.rupress.org/content/194/10/1433.full.pdf |
| Alternate Webpage(s) | http://ftp.ncbi.nlm.nih.gov/pub/pmc/6f/ba/011229.PMC2193680.pdf |
| Alternate Webpage(s) | http://jem.rupress.org/content/jem/194/10/1433.full.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acute GVH disease Apoptosis Bone Marrow Transplantation Graft versus host disease prophylaxis/therapy Histopathology Interleukins Leukemia, B-Cell Leukemia, Myelocytic, Acute Lipopolysaccharides Neoplasms Recombinant Interferon-gamma T-Lymphocyte Transplanted tissue Tumor Necrosis Factor-alpha cell growth cytokine |
| Content Type | Text |
| Resource Type | Article |
