Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat.
Interleukin-1 (IL-1) synthesis in the brain is stimulated by mechanical injury and IL-1 mimics some effects of injury, such as gliosis and neovascularization. We report that neuronal death resulting from focal cerebral ischaemia (middle cerebral artery occlusion, 24 h) is significantly inhibited (by 50%) in rats injected with a recombinant IL-1 receptor antagonist (IL-1ra, 10 micrograms, icv 30 min before and 10 min after ischaemia). Excitotoxic damage due to striatal infusion of an NMDA-receptor agonist (cis-2,4-methanoglutamate) was also markedly inhibited (71%) by injection of the IL-1ra. These data indicate that endogenous IL-1 is a mediator of ischaemic and excitotoxic brain damage, and that inhibitors of IL-1 action may be of therapeutic value in the treatment of acute or chronic neuronal death.
Relton
J K
JK
Department of Physiological Sciences, University of Manchester, UK.
Rothwell
N J
NJ
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002545:Brain Ischemia / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D002536:Cerebral Arteries / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013238:Stereotaxic Techniques
D005971:Glutamates; D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C066302:2,4-methanoglutamate