Emerging cytokine targets in rheumatoid arthritis

Curr Opin Rheumatol. 2007 May;19(3):246-51. doi: 10.1097/BOR.0b013e3280eec78c.

Abstract

Purpose of review: The utility of cytokines as therapeutic targets in rheumatoid arthritis has been unequivocally demonstrated by the success of tumour necrosis factor blockade in clinical practice. Partial and non-responses to tumour necrosis factor blocking agents, however, together with the increasing clinical drive to remission induction, requires that further therapeutic targets be identified.

Recent findings: Numerous cytokine activities with pathogenetic potential have now been demonstrated in rheumatoid arthritis synovial membrane, including members of the IL-1 superfamily and the IL-12 superfamily. Continued efforts are ongoing to target IL-6 and IL-15 in clinical trials with promising data emerging. There is particular interest in the biology of IL-17 and of the recently described IL-32 as critical effector mediators.

Summary: Novel cytokine activities are emerging on an ongoing basis. There remain difficulties in ascribing the optimal regulatory hierarchy for given moieties on the basis of existing preclinical model systems. This in turn poses novel challenges in determining which cytokines represent the best therapeutic targets.

Publication types

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

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / therapy*
  • Cytokines / antagonists & inhibitors*
  • Cytokines / metabolism
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-15 / metabolism
  • Interleukin-23 / metabolism
  • Interleukin-6 / metabolism
  • Interleukins / metabolism
  • Models, Immunological
  • Signal Transduction

Substances

  • Cytokines
  • IL32 protein, human
  • IL6 protein, human
  • Interleukin-1
  • Interleukin-15
  • Interleukin-23
  • Interleukin-6
  • Interleukins
  • Interleukin-12