IL-23 Blockade for Crohn s disease: next generation of anti-cytokine therapy

Expert Rev Clin Immunol. 2017 May;13(5):457-467. doi: 10.1080/1744666X.2017.1279055. Epub 2017 Jan 13.

Abstract

Adaptive immunity in intestinal inflammation may play a key role in the pathogenesis of Crohn's disease. In particular, interleukin (IL)-23 may be a key mediator in chronic intestinal inflammation by inducing the differentiation of naïve CD4 + T cells into Th17, with the production of several pro-inflammatory cytokines. Furthermore, IL-23 induces interferon-γ (IFN- γ) production from activated T cells, a critical cytokine in innate and adaptive immunity against infections. Areas covered: We aim to review the available data from literature regarding the role of IL-23, with a more specific focus on the recent progresses in the therapeutic modulation of this cytokine. Expert commentary: Increased knowledge regarding the role of IL-23 has allowed for the development of effective therapeutic progresses by blocking the IL-23 mediated pathways. Primary or secondary loss of response to anti-TNF therapies in Crohn's disease patients during the first year is widely described in literature: the development of new drugs, with alternative mechanisms of action, is thus a key point to consider for the optimal management of these subjects. Drugs blocking the IL-12/23 pathway showed a good efficacy and safety profile in immune-mediated diseases Further studies are necessary regarding the role of the single blockade of IL-23.

Keywords: Crohn’s disease; anti-cytokine; biologics; interleukin-23; ustekinumab.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Blocking / therapeutic use*
  • Crohn Disease / immunology
  • Crohn Disease / therapy*
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / metabolism*
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism*
  • Signal Transduction
  • Th17 Cells / immunology*
  • Ustekinumab / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Blocking
  • Inflammation Mediators
  • Interleukin-23
  • Interleukin-12
  • Interferon-gamma
  • Ustekinumab