Impact of interleukin-6 classic- and trans-signaling on liver damage and regeneration

J Autoimmun. 2010 Feb;34(1):29-37. doi: 10.1016/j.jaut.2009.08.003. Epub 2009 Aug 29.


Interleukin-6 (IL-6) has been suggested to play a pivotal role in liver regeneration. IL-6 on target cells activates a receptor complex consisting of the IL-6 receptor (IL-6R) and the signal transducing receptor subunit gp130. Not all cells in the body express the IL-6R on the cell surface. IL-6 can signal via two different pathways: classical signaling via the membrane bound IL-6R and IL-6 trans-signaling via a naturally occurring soluble IL-6R (sIL-6R). This second pathway widens the scope of IL-6 signaling since also cells expressing no membrane bound IL-6R can be stimulated by the trans-signal pathway. Mimicking IL-6 trans-signaling via a designer molecule, Hyper-IL-6 has been shown to accelerate liver regeneration. Another designer molecule, sgp130Fc, specifically blocks IL-6 trans-signaling. Using these proteins we investigated the contribution of IL-6 classic- and trans-signaling in the liver. Here we review the role of IL-6 signaling in response to liver damage and during liver regeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Apoptosis / immunology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Cytokine Receptor gp130 / immunology
  • Cytokine Receptor gp130 / metabolism
  • Humans
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Liver / immunology
  • Liver / metabolism*
  • Liver / pathology
  • Liver Regeneration / immunology
  • Receptors, Interleukin-6 / immunology
  • Receptors, Interleukin-6 / metabolism
  • Signal Transduction / immunology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • Receptors, Interleukin-6
  • Cytokine Receptor gp130
  • tocilizumab