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

FASEB J. 2000 Oct;14(13):1979-87. doi: 10.1096/fj.99-0913com.

Abstract

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 severe human liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Disease Models, Animal
  • Galactosamine / toxicity
  • Humans
  • Interleukin-6 / agonists*
  • Interleukin-6 / therapeutic use*
  • Liver Failure / drug therapy*
  • Liver Regeneration / drug effects*
  • Male
  • Rats
  • Rats, Inbred F344
  • Receptors, Interleukin / therapeutic use*
  • Receptors, Interleukin-6
  • Recombinant Fusion Proteins / therapeutic use
  • Thioacetamide / toxicity

Substances

  • Interleukin-6
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Recombinant Fusion Proteins
  • interleukin 6-interleukin 6 receptor fusion protein, recombinant
  • Thioacetamide
  • Galactosamine