title: Interleukin-1 receptor antagonist inhibits neuronal damage caused by fluid percussion injury in the rat.
abstract: Increased expression of the cytokine interleukin-1 (IL-1) has been observed in rodent and human brain after injury, and IL-1 has been implicated in ischaemic and excitotoxic brain damage in the rat. These data suggest that neurodegeneration caused by brain injury may be mediated by local IL-1 production and action. This hypothesis was tested by studying the effects of central injection of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) on brain damage (assessed histologically, H and E stain) induced by fluid percussion trauma in the rat. Injection of rhIL-1ra (10 micrograms, i.c.v.) 15 min and 2, 4, 6, 8, 24 and 48 h after injury significantly reduced, by 44%, the extent of damage measured 3 days later. Similar protection was observed in animals killed 7 days after injury. Delayed administration of rhIL-1ra (4, 6, 8, 24 and 48 h) after injury also significantly reduced (by 28%) neuronal damage. These data indicate that endogenous IL-1 mediates damage caused by traumatic brain injury and that rhIL-1ra offers significant protection even when treatment is delayed.
authors.affiliation: University of Manchester, School of Biological Sciences, UK.
authors.forename: S
authors.initials: S
authors.lastname: Toulmond
authors.forename: N J
authors.initials: NJ
authors.lastname: Rothwell
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins