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

被引:67
作者
Bozza, M
Bliss, JL
Maylor, R
Erickson, J
Donnelly, L
Bouchard, P
Dorner, AJ
Trepicchio, WL [1 ]
机构
[1] Inst Genet, Dept Mol Med, Andover, MA 01810 USA
[2] Inst Genet, Dept Lab Anim Sci, Andover, MA 01810 USA
[3] Inst Genet, Dept Safety Assessment, Andover, MA 01810 USA
关键词
D O I
10.1002/hep.510300616
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 gamma (IFN-gamma) 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 alpha (TNF-alpha), and IFN-gamma 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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页码:1441 / 1447
页数:7
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