The present study was attempted to determine whether interleukin-1 receptor antagonist (IL-1ra) pretreatment exerts its antipyresis by reducing organum vasculosum laminae terminalis (OVLT) release of glutamate, hydroxyl radicals and prostaglandin E2 in rabbits. It was found that systemic administration of lipopolysaccharide induced increased levels of both core temperature and OVLT levels of glutamate, hydroxyl radicals, and prostaglandin E2. The rise in both the core temperature and OVLT glutamate, hydroxyl radicals and prostaglandin E2 could also be induced by intracerebroventricular injection of interleukin-1β. Pretreatment with an intracerebroventricular dose of IL-1ra significantly prevented the lipopolysaccharide or IL-1β-induced overproduction of glutamate, hydroxyl radicals, and prostaglandin E2 in OVLT of rabbit's brain. The febrile response caused by systemic administration of lipopolysaccharide or central injection of interleukin-1β could also be IL-1ra pretreatment-ameliorated. These results indicate that IL-1ra pretreatment may exert its antipyresis by inhibiting the glutamate–hydroxyl radicals–prostaglandin E2 pathways in the OVLT of rabbit's brain during lipopolysaccharide fever.
關聯:
European Journal of Pharmacology
629(1-2)：p.125-131
