After interleukin-12p40, are interleukin-23 and interleukin-17 the next therapeutic targets for inflammatory bowel disease?

Int Immunopharmacol. 2007 Apr;7(4):409-16. doi: 10.1016/j.intimp.2006.09.024. Epub 2006 Nov 13.

Abstract

Inflammatory bowel disease (IBD), typified by Crohn's disease and ulcerative colitis, is a common disorder characterized by recurrent and serious inflammation of the gastrointestinal tract. Recent immunologic advances have established that T cells and inflammatory cytokines play a pivotal role in the gastrointestinal inflammation of IBD. However, many cytokines not only elicit inflammation but also protect host against microbial invasion. Hence, suppression of these dual-purpose cytokines often exposes the patients to significant risk of infection. Recent research on Interleukin (IL)-23, IL-17, and IL-17 producing T cells has become the vanguard of further understanding the contribution of cytokines to autoimmune and inflammatory diseases. IL-23 is a newly discovered member of the IL-12-related cytokine family, and is primarily involved in the differentiation of pathogenic T cells characterized by their production of IL-17. IL-17 is a potent inflammatory mediator implicated in a number of autoimmune diseases. The discovery of this IL-23/IL-17-mediated inflammatory axis is having a profound impact on the elucidation of T cell-mediated pathogenesis as well as development of novel therapeutic targets. In this review, we discuss the current literature and present our recent studies on the role of IL-23 and IL-17 in the pathogenesis of IBD. Controlling the expression/production of IL-23 and IL-17 is an approach that would allow the development of a novel treatment strategy with more anti-inflammatory efficacy and potentially with less suppressive effects on host defenses.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • Clinical Trials as Topic
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / immunology*
  • Interleukin-12 Subunit p40 / immunology*
  • Interleukin-17 / immunology*
  • Interleukin-23 / immunology*

Substances

  • Antibodies, Monoclonal
  • Interleukin-12 Subunit p40
  • Interleukin-17
  • Interleukin-23