Interleukin-1 receptor antagonist inhibits the release of glutamate, hydroxyl radicals, and prostaglandin E 2 in the hypothalamus during pyrogen-induced fever in rabbits

Abstract

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 E 2 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 E 2. The rise in both the core temperature and OVLT glutamate, hydroxyl radicals and prostaglandin E 2 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 E 2 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 E 2 pathways in the OVLT of rabbit's brain during lipopolysaccharide fever.