Endogenous interleukin-1 receptor antagonist is neuroprotective.
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.
Loddick
S A
SA
School of Biological Sciences, University of Manchester, United Kingdom.
Wong
M L
ML
Bongiorno
P B
PB
Gold
P W
PW
Licinio
J
J
Rothwell
N J
NJ
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins