Interleukin-1 receptor antagonist inhibits the release of glutamate, hydroxyl radicals, and prostaglandin E(2) in the hypothalamus during pyrogen-induced fever in rabbits.
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-1beta. Pretreatment with an intracerebroventricular dose of IL-1ra significantly prevented the lipopolysaccharide or IL-1beta-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-1beta 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.
Huang
Kuo-Feng
KF
Department of Plastic Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan.
Huang
Wu-Tein
WT
Lin
Kao-Chang
KC
Lin
Mao-Tsun
MT
Chang
Ching-Ping
CP
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism*; D005334:Fever / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007267:Injections; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011749:Pyrogens / Q000494:pharmacology*; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013997:Time Factors
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011749:Pyrogens; D017472:Receptors, Interleukin-1; D017665:Hydroxyl Radical; D018698:Glutamic Acid; D015232:Dinoprostone