Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases

Nat Rev Drug Discov. 2012 Aug;11(8):633-52. doi: 10.1038/nrd3800.

Abstract

Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / physiopathology
  • Drug Delivery Systems
  • Drug Design
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / metabolism
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Receptors, Interleukin-1 / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use
  • Severity of Illness Index

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Receptors, Interleukin-1
  • Recombinant Fusion Proteins
  • canakinumab
  • rilonacept