Department of Plastic Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan.
Eur J Pharmacol. 2010 Mar 10;629(1-3):125-31. doi: 10.1016/j.ejphar.2009.11.060. Epub 2009 Dec 1.
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.
本研究旨在探讨白细胞介素-1 受体拮抗剂 (IL-1ra) 预处理是否通过降低终脑室 (OVLT) 释放谷氨酸、羟自由基和前列腺素 E2 来发挥解热作用。结果发现，脂多糖全身给药可引起核心体温和 OVLT 水平的谷氨酸、羟自由基和前列腺素 E2 水平升高。白细胞介素-1β脑室内注射也可引起核心体温和 OVLT 谷氨酸、羟自由基和前列腺素 E2 的升高。IL-1ra 脑室内预处理可显著预防脂多糖或白细胞介素-1β诱导的兔脑 OVLT 中谷氨酸、羟自由基和前列腺素 E2 的过度产生。脂多糖全身给药或白细胞介素-1β 中枢注射引起的发热反应也可被 IL-1ra 预处理减轻。这些结果表明，IL-1ra 预处理可能通过抑制脂多糖发热期间兔脑 OVLT 中的谷氨酸-羟自由基-前列腺素 E2 途径发挥解热作用。
