Endogenous interleukin-1 receptor antagonist is neuroprotective

Biochem Biophys Res Commun. 1997 May 8;234(1):211-5. doi: 10.1006/bbrc.1997.6436.

Abstract

Interleukin-1 (IL-1) has been implicated in chronic and acute cerebral neuropathologies. IL-1 receptor antagonist (IL-1ra), a naturally occurring protein that binds to IL-1 receptors without inducing signal transduction, blocks several actions of IL-1. IL-1ra acts at the local level and it also circulates in the bloodstream. We now report evidence for a biological function of IL-1ra in the brain as an endogenous neuroprotective molecule. Cerebral expression of IL-1ra mRNA is induced rapidly by focal cerebral ischemia in rats, and inhibition of the action of IL-1ra, by passive immuno-neutralization, markedly enhances ischemic damage. To our knowledge this is the first report of an action of endogenous IL-1ra in the brain. Control of IL-1ra expression or action may therefore provide a useful therapeutic strategy to limit acute neurodegeneration.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Brain / metabolism
  • Brain / pathology*
  • Gene Expression Regulation
  • In Situ Hybridization
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / pharmacology
  • Ischemic Attack, Transient / metabolism
  • Ischemic Attack, Transient / pathology*
  • Male
  • Neuroprotective Agents*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / immunology
  • Sialoglycoproteins / physiology*

Substances

  • Antibodies
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Neuroprotective Agents
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Sialoglycoproteins