4.7 Article

Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury

Journal

FASEB JOURNAL
Volume 14, Issue 13, Pages 1979-1987

Publisher

FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.99-0913com

Keywords

interleukin 6; chimeric protein; hyper-IL-6; cytokines; hepatotoxicity; liver failure

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The cytokine IL-6 plays a significant role in liver regeneration in conjunction with additional growth factors (HGF, TNF-alpha, and TGF-alpha). Many IL-6 effects depend on a naturally occurring soluble IL-6 receptor (sIL-6R). Here, the chimeric protein hyper-IL-6, constructed from the human IL-6 protein fused to a truncated form of its receptor, was found to have superagonistic IL-6 properties, and as such, enhanced liver cell regeneration. Hyper-IL-6 reversed the state of hepatotoxicity and enhanced the survival rates of rats suffering from fulminant hepatic failure after D-galactosamine administration. The hyper-IL-6 protein has a significant potential for use in the treatment of set ere human liver diseases.

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