INTERLEUKIN-11 PROMOTES T-CELL POLARIZATION AND PREVENTS ACUTE GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Administration of IL-11 prevented lethal graft-versus-host disease (GV HD) in a murine bone marrow transplant (BMT) model (B6 --> B6D2F1) acr oss MHC and minor I-I antigen barriers (survival at day 50: 90 vs 20%, P < 0.001), Surpisingly, IL-11 administration polarized the donor T c ell cytokine responses to host antigen after BMT with a 50% reduction in IFN gamma and IL-2 secretion and a 10-fold increase in IL-4. This p olarization of T cell responses was associated with reduced IFN gamma serum levels and decreased IL-12 production in mixed lymphocyte cultur es (MLC), In addition, IL-11 prevented small bowel damage and reduced serum endotoxin levels by 80%. Treatment with IL-11 also reduced TNF a lpha serum levels and suppressed TNF alpha secretion by macrophages to LPS stimulation in vitro. IL-11 thus decreased GVHD morbidity and mor tality by three mechanisms: (a) polarization of donor T cells; (b) pro tection of the small bowel; and (c) suppression of inflammatory cytoki nes such as TNF alpha. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory pr ocesses such as GVHD.