Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development

Semin Immunol. 2014 Feb;26(1):75-9. doi: 10.1016/j.smim.2013.12.003. Epub 2014 Jan 18.

Abstract

IL-6 signaling is of central importance for the maintenance of chronic intestinal inflammation in inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. IL-6 regulates T cell differentiation, activation and resistance against apoptosis and thereby controls the balance between pro-inflammatory T cell subsets such as Th1 or Th17 cells and immunosuppressive regulatory T cells. Furthermore, IL-6 has been implicated in the pathogenesis of colorectal cancer (CRC). In fact, IL-6 directly promotes tumor cell proliferation and survival through STAT3 activation. Due to its role in both types of diseases, IL-6 has been proposed as a missing link between inflammation and tumor development. During recent years, several therapeutics targeting IL-6 dependent pathways have been developed. Although clinical data about anti-IL-6 treatment in intestinal diseases are currently scarce, targeting this pathway might be a promising strategy in IBD and CRC.

Keywords: Colorectal cancer; Crohn's disease; Cytokines; Inflammatory bowel disease; Interleukin-6; JAK; SOCS3; STAT3; Ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Molecular Targeted Therapy
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Interleukin-6
  • STAT3 Transcription Factor