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

The cytokine IL‐6 plays a significant role in liver regeneration in conjunction with additional growth factors (HGF, TNF‐a, and TGF‐a). 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‐galac‐tosamine administration. The hyper‐IL‐6 protein has a significant potential for use in the treatment of severe human liver diseases.—Galun, E., Zeira, E., Pappo, O., Peters, M., Rose‐John, S. Liver regeneration induced by a designer human IL‐6/sIL‐6R fusion protein reverses severe hepatocellular injury. FASEB J. 14, 1979–1987 (2000)