Neuroprotective Effects of Human Recombinant Interleukin-1 Receptor Antagonist in Focal Cerebral Ischaemia in the Rat

• Published in: Journal of cerebral blood flow and metabolism 1996-09, Vol.16 (5), p.932-940
• Main Authors: Loddick, Sarah A., Rothwell, Nancy J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Pressure; Cerebral Cortex - pathology; Corpus Striatum - pathology; Heart Rate; Humans; Injections, Intraventricular; Interleukin 1 Receptor Antagonist Protein; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - pathology; Male; Medical sciences; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1 - antagonists & inhibitors; Recombinant Proteins - pharmacology; Sialoglycoproteins - administration & dosage; Sialoglycoproteins - therapeutic use
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-199609000-00017

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-1β or rhIL-1ra on ischaemia damage and physiological parameters after permanent middle cerebral artery occlusion in the rat. IL-1β (5 ng, i.c.v.) markedly (92%) enhanced infarct volume and caused a significant rise in body temperature, but rhIL-1ra (10 μg, 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.