IL-12 as a therapeutic target for pharmacological modulation in immune-mediated and inflammatory diseases: regulation of T helper 1/T helper 2 responses

Br J Pharmacol. 1999 Jul;127(6):1295-304. doi: 10.1038/sj.bjp.0702689.

Abstract

Interleukin-12 (IL-12) is a pivotal cytokine in driving the immune system towards a T helper (Th)1 type response and preventing a Th2 type immune profile. Therefore, IL-12 is indispensable in the defense against certain, mainly intracellular pathogens, but overproduction of this cytokine is crucially involved in the etiology of several inflammatory and autoimmune diseases. Hence, IL-12 is an ideal target for pharmacological intervention in the therapy of autoimmune and inflammatory diseases. The production of IL-12 and a resultant Th1 type immune response can be suppressed with several pharmacological approaches including modulation of intracellular cyclic AMP levels, glucocorticoids and nuclear factor-kappaB inhibition. IL-12 responsiveness may be inhibited using anti-IL-12 antibodies, soluble IL-12 receptors or the IL-12 p40 homodimer. Exploitation of these approaches may provide novel means for the experimental therapy of a variety of pathophysiological states.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / biosynthesis
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • Interleukin-12