Interleukin-11 promotes T cell polarization and prevents acute graff- versus-host disease after allogeneic bone marrow transplantation

Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a murine bone marrow transplant (BMT) model (B6 → B6D2F1) across MHC and minor H antigen barriers (survival at day 50:90 vs 20%, P < 0.001). Surprisingly, IL-11 administration polarized the donor T cell cytokine responses to host antigen after BMT with a 50% reduction in IFNγ and IL-2 secretion and a 10-fold increase in IL-4. This polarization of T cell responses was associated with reduced IFNγ serum levels and decreased IL-12 production in mixed lymphocyte cultures (MLC). In addition, IL-11 prevented small bowel damage and reduced serum endotoxin levels by 80%. Treatment with IL-11 also reduced TNFα serum levels and suppressed TNFα secretion by macrophages to LPS stimulation in vitro. IL-11 thus decreased GVHD morbidity and mortality by three mechanisms: (a) polarization of donor T cells; (b) protection of the small bowel; and (c) suppression of inflammatory cytokines such as TNFα. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD.