NEUROPROTECTIVE EFFECTS OF HUMAN RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST IN FOCAL CEREBRAL-ISCHEMIA IN THE RAT

Recombinant human interleukin-l receptor antagonist (rhIL-1ra) markedl y protects against focal cerebral ischaemia in the rat, implicating en dogenous IL 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 phys iological parameters after permanent middle cerebral artery occlusion in the rat. IL-1 beta (5 ng, i.c.v.) markedly (92%) enhanced infarct v olume and caused a significant rise in body temperature, but rhIL-1ra (10 mu g, i.c.v.) significantly reduced infarct volume and did not sig nificantly affect heart rate, blood pressure, or body temperature. rhI L-1ra administered 30 min before, or at the time of ischaemia signific antly reduced infarct volume in cortex (55 and 60%, respectively) and striatum (57 and 41%, respectively). rhIL-1ra administered 30 min afte r ischaemia significantly reduced total and cortical infarct volume (2 6 and 29%, respectively), but did not significantly protect striatal t issue. The effects of rhIL-1ra were still evident in both cortex and s triatum 7 days after ischaemia. These results support the role of IL-1 in ischaemic brain damage, revealing potent, sustained, neuroprotecti ve effects of rhIL-1ra in the cortex and striatum, which cannot be att ributed directly to changes in physiological parameters.