Interleukin-11 reduces T-cell-dependent experimental liver injury in mice

Recombinant human interleukin-11 (rhIL-11) is a multifunctional cytokine th at can reduce inflammation through the downregulation of multiple pro-infla mmatory mediators from activated macrophages. rhIL-11 also inhibits product ion of several immunostimulatory cytokines such as IL-12 and interferon gam ma (IFN-gamma) and has shown biological activity in multiple animal models of inflammatory disease consistent with immunomodulatory effects on macroph ages and T cells. To further elucidate the anti-inflammatory activity of rh IL-11 in vivo, the effect of rhIL-11 in a model of Concanavalin A (Con-A)-i nduced T-cell-mediated hepatotoxicity was examined. Administration of a sin gle dose of rhIL-11 before Con-A administration reduced centrilobular liver necrosis and enhanced survival. A dose-dependent reduction in serum levels of liver enzymes, tumor necrosis factor alpha (TNF-alpha), and IFN-gamma c orresponded with this amelioration of liver damage. No significant change i n infiltrating lymphocyte populations in the liver was observed following r hIL-11 treatment. Taken together, these results indicate that rhIL-11 ameli orates T-cell-mediated hepatic injury and suggests its therapeutic potentia l to treat inflammatory liver disease.