Interleukin-6 trans-signaling in inflammatory bowel disease

Cytokine Growth Factor Rev. 2006 Dec;17(6):451-61. doi: 10.1016/j.cytogfr.2006.09.003. Epub 2006 Oct 12.


The pathogenesis of inflammatory bowel disease (IBD) is complex, involving a wide range of molecules including cytokines. Recent investigations support the important role of an interleukin-6 (IL-6) signaling pathway in the development of IBD. However, the molecular mechanisms of this pathway in the intestine remain incompletely understood. The circulating and intestinal levels of IL-6 as well as soluble IL-6 receptor (sIL-6R) are increased in patients with IBD. It is remarkable that the mucosal T cells of IBD patients are extremely resistant to apoptosis and that a large fraction of these cells express membrane-bound gp130 but not IL-6R. The accumulated evidence strongly supports the hypothesis that the development and perpetuation of IBD relies on the increased formation of IL-6/sIL-6R complexes interacting with membrane-bound gp130 on T cells via trans-signaling. These studies suggest that IL-6 trans-signaling may play a role in the development of IBD; they therefore imply the possibility of a selective therapeutic strategy to target this signaling.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Cell Movement
  • Colorectal Neoplasms / etiology
  • Cytokine Receptor gp130 / pharmacology
  • Cytokine Receptor gp130 / physiology
  • Humans
  • Inflammatory Bowel Diseases / etiology*
  • Inflammatory Bowel Diseases / physiopathology
  • Inflammatory Bowel Diseases / therapy
  • Interleukin-6 / physiology
  • Leukocytes / pathology
  • Leukocytes / physiology
  • Mice
  • Models, Biological
  • Receptors, Interleukin-6 / physiology*
  • STAT3 Transcription Factor / physiology
  • Signal Transduction


  • IL6 protein, human
  • Interleukin-6
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Cytokine Receptor gp130