Redeeming an old foe: protective as well as pathophysiological roles for tumor necrosis factor in inflammatory bowel disease

Am J Physiol Gastrointest Liver Physiol. 2015 Feb 1;308(3):G161-70. doi: 10.1152/ajpgi.00142.2014. Epub 2014 Dec 4.

Abstract

Tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are major therapeutic targets for inflammatory bowel disease. Research advances have demonstrated that TNF produces pleiotropic responses in the gastrointestinal (GI) tract. Although in excess TNF can contribute to GI pathology, TNF is also a critical protective factor to promote GI homeostasis following injury and inflammation. Genetic studies using candidate and genome-wide association study approaches have identified variants in TNF or its receptors that are associated with Crohn's disease or ulcerative colitis in multiple populations, although the basis for these associations remains unclear. This review considers the efficacy and mechanism of anti-TNF therapies for inflammatory bowel disease to reconcile the many disparate aspects of TNF research and to consider the potential protective effects of TNF signaling in GI health.

Keywords: inflammatory bowel disease; tumor necrosis factor; tumor necrosis factor receptor 1; tumor necrosis factor receptor 2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Gastrointestinal Agents / therapeutic use
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / metabolism
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Receptors, Tumor Necrosis Factor / immunology
  • Tumor Necrosis Factors / immunology*
  • Tumor Necrosis Factors / metabolism

Substances

  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factors