Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat

J Cereb Blood Flow Metab. 1996 Sep;16(5):932-40. 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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • 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
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Recombinant Proteins / pharmacology
  • Sialoglycoproteins / administration & dosage
  • Sialoglycoproteins / therapeutic use*


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Sialoglycoproteins