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

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Abstract

Recombinant human interleukin-11 (rhIL-11) is a multifunctional cytokine that can reduce inflammation through the downregulation of multiple pro-inflammatory mediators from activated macrophages. rhIL-11 also inhibits production of several immunostimulatory cytokines such as IL-12 and interferon γ (IFN-γ) and has shown biological activity in multiple animal models of inflammatory disease consistent with immunomodulatory effects on macrophages and T cells. To further elucidate the anti-inflammatory activity of rhIL-11 in vivo, the effect of rhIL-11 in a model of Concanavalin A (Con-A)–induced T-cell–mediated hepatotoxicity was examined. Administration of a single 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 α (TNF-α), and IFN-γ corresponded with this amelioration of liver damage. No significant change in infiltrating lymphocyte populations in the liver was observed following rhIL-11 treatment. Taken together, these results indicate that rhIL-11 ameliorates T-cell–mediated hepatic injury and suggests its therapeutic potential to treat inflammatory liver disease.

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