The inflammasome and IL-1β: implications for the treatment of inflammatory diseases

Immunotherapy. 2015;7(3):243-54. doi: 10.2217/imt.14.106.

Abstract

The bioactive form of IL-1β, a key immunoregulatory and proinflammatory cytokine, is produced by the inflammasome - a caspase-1 activating molecular platform - in response to selected danger-associated molecular patterns and pathogen-associated molecular patterns. Advances in understanding the role of IL-1β in inflammatory conditions has resulted in IL-1β becoming a therapeutic target for a number of inflammatory diseases beyond the rare monogenic autoinflammatory diseases characterized by aberrant inflammasome function and enhanced bioactive IL-1β production. In the monogenic autoinflammatory diseases known as cryopyrin-associated periodic syndromes, neutralization of IL-1β results in a rapid and sustained reduction in disease severity without severe side effects, which has consequently driven off-label applications of IL-1β-targeted therapy in other inflammatory diseases. This review summarizes inflammatory diseases for which accumulating evidence suggests a therapeutic potential for IL-1β antagonists.

Keywords: IL-1β; anakinra; autoinflammatory disease; canakinumab; caspase-1; inflammasome; inflammation; rilonacept.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Blocking / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Caspase 1 / metabolism
  • Cryopyrin-Associated Periodic Syndromes / immunology
  • Cryopyrin-Associated Periodic Syndromes / therapy*
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation / immunology
  • Inflammation / therapy*
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1beta / metabolism*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Inflammasomes
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • canakinumab
  • Caspase 1