Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat.
Recombinant human interleukin-1 receptor antagonist (rhIL-1ra) markedly protects against focal cerebral ischaemia in the rat, implicating endogenous IL-1 in the events leading to cerebral infarction. The present experiments investigated the effect of intracerebroventricular (i.c.v.) administration of IL-1 beta or rhIL-1ra on ischaemia damage and physiological parameters after permanent middle cerebral artery occlusion in the rat. IL-1 beta (5 ng. i.c.v.) markedly (92%) enhanced infarct volume and caused a significant rise in body temperature, but rhIL-1ra (10 micrograms, i.c.v.) significantly reduced infarct volume and did not significantly affect heart rate, blood pressure, or body temperature, rhIL-1ra administered 30 min before, or at the time of ischaemia significantly reduced infarct volume in cortex (55 and 60%, respectively) and striatum (52 and 41%, respectively). rhIL-1ra administered 30 min after ischaemia significantly reduced total and cortical infarct volume (26 and 29%, respectively), but did not significantly protect striatal tissue. The effects of rhIL-1ra were still evident in both cortex and striatum 7 days after ischaemia. These results support the role of IL-1 in ischaemic brain damage, revealing potent, sustained, neuroprotective effects of rhIL-1ra in the cortex and striatum, which cannot be attributed directly to changes in physiological parameters.
Loddick
S A
SA
School of Biological Sciences, University of Manchester, England.
Rothwell
N J
NJ
D000818:Animals; D001794:Blood Pressure; D002540:Cerebral Cortex / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D006339:Heart Rate; D006801:Humans; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins