Is IL-1 a good therapeutic target in the treatment of arthritis?

Best Pract Res Clin Rheumatol. 2006 Oct;20(5):879-96. doi: 10.1016/j.berh.2006.06.004.


Inflammation is an important homeostatic mechanism that limits the effects of infectious agents. However, inflammation might be self-damaging and therefore has to be tightly controlled or even abolished by the organism. Interleukin 1 (IL-1) is a crucial mediator of the inflammatory response, playing an important part in the body's natural responses and the development of pathological conditions leading to chronic inflammation. While IL-1 production may be decreased or its effects limited by so-called anti-inflammatory cytokines, in vitro IL-1 inflammatory effects are inhibited and can be abolished by one particularly powerful inhibitor, IL-1 receptor antagonist (IL-1Ra). Recent research has shown that in the processes of rheumatoid arthritis (RA) IL-1 is one of the pivotal cytokines in initiating disease, and IL-1Ra has been shown conclusively to block its effects. In laboratory and animal studies the inhibition of IL-1 by either antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. Because of its beneficial effects in many animal disease models, IL-1Ra has been used as a therapeutic agent in human patients. The recombinant form of IL-1Ra, anakinra (Kineret, Amgen) failed to show beneficial effects in septic shock and displays weak effects in RA patients. However, IL-1 blockade by anakinra is dramatically effective in systemic-onset juvenile idiopathic arthritis, in adult Still's disease and in several autoinflammatory disorders, most of the latter being caused by mutations of proteins controlling IL-1beta secretion. Importantly, to be efficacious, anakinra required daily injections, suggesting that administered IL-1Ra displays very short-term effects. Better IL-1 antagonists are in the process of being developed.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis / drug therapy*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / physiopathology
  • Disease Models, Animal
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / physiology
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / physiology
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Receptors, Interleukin / antagonists & inhibitors
  • Receptors, Interleukin / drug effects
  • Receptors, Interleukin / physiology


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-1beta
  • Receptors, Interleukin