IL-1 pathways in inflammation and human diseases

Nat Rev Rheumatol. 2010 Apr;6(4):232-41. doi: 10.1038/nrrheum.2010.4. Epub 2010 Feb 23.


Interleukin (IL)-1 was first cloned in the 1980s, and rapidly emerged as a key player in the regulation of inflammatory processes. The term IL-1 refers to two cytokines, IL-1alpha and IL-1beta, which are encoded by two separate genes. The effects of IL-1 are tightly controlled by several naturally occurring inhibitors, such as IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type II (IL-1RII), and other soluble receptors. Numerous IL-1 inhibitors have been developed and tested primarily in rheumatoid arthritis, with only modest effects. By contrast, the use of IL-1 antagonists has been uniformly associated with beneficial effects in patients with hereditary autoinflammatory conditions associated with excessive IL-1 signaling, such as cryopyrinopathies and IL-1Ra deficiency. Successful treatment with IL-1 blockers has also been reported in other hereditary autoinflammatory diseases, as well as in nonhereditary inflammatory diseases, such as Schnizler syndrome, systemic-onset juvenile idiopathic arthritis and adult Still disease. The role of microcrystals in the regulation of IL-1beta processing and release has provided the rationale for the use of IL-1 inhibitors in crystal-induced arthritis. Finally, preliminary results indicating that IL-1 targeting is efficacious in type 2 diabetes and smoldering myeloma have further broadened the spectrum of IL-1-driven diseases.

Publication types

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

MeSH terms

  • Animals
  • Cohort Studies
  • Disease Models, Animal
  • Drug Delivery Systems
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / physiopathology
  • Inflammation Mediators / blood
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / metabolism*
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Prognosis
  • Receptors, Interleukin / antagonists & inhibitors
  • Receptors, Interleukin / drug effects
  • Rheumatic Diseases / blood*
  • Rheumatic Diseases / diagnosis
  • Rheumatic Diseases / drug therapy*
  • Risk Assessment
  • Signal Transduction
  • Treatment Outcome


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