Inflammasome and cytokine blocking strategies in autoinflammatory disorders

Clin Immunol. 2013 Jun;147(3):242-75. doi: 10.1016/j.clim.2013.04.008. Epub 2013 Apr 19.

Abstract

Autoinflammatory disorders are characterized by usually unprovoked recurrent episodes of features of inflammation caused by activation of the innate immune system. Many autoinflammatory disorders - the monogenetic defects in particular - are associated with alterations of inflammasomes. Inflammasomes are complex multimolecular structures, which respond to "danger" signals by activation of cytokines. Among these, IL-1 is the key player of the innate immune response and inflammation. Consequently, IL-1 blocking strategies are specific pathway targeting therapies in autoinflammatory diseases and applied in CAPS, colchicine-resistant FMF, TRAPS, HIDS and DIRA. A number of rare genetic disorders involve inflammasome malfunction resulting in enhanced inflammatory response. IL-1 inhibition to date is the most successful specific therapy in autoinflammatory disorders. Here, current treatment strategies in autoinflammatory disorders are reviewed with a focus on inflammasome and cytokine inhibition.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antirheumatic Agents / pharmacology
  • Enzyme Activation
  • Hereditary Autoinflammatory Diseases / drug therapy*
  • Hereditary Autoinflammatory Diseases / immunology
  • Humans
  • Inflammasomes / antagonists & inhibitors*
  • Inflammasomes / immunology
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / immunology
  • NF-kappa B p50 Subunit / metabolism
  • Recombinant Fusion Proteins / pharmacology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Inflammasomes
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Recombinant Fusion Proteins
  • canakinumab
  • rilonacept
  • gevokizumab