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). Surpisingly,
IL-11 administration polarized the donor T cell
cytokine responses to host
antigen after BMT with a 50% reduction in IFNgamma and
IL-2 secretion and a 10-fold increase in
IL-4. This polarization of T cell responses was associated with reduced IFNgamma 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
TNFalpha serum levels and suppressed
TNFalpha 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
TNFalpha. We conclude that brief treatment with
IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD.