Brain sites of action of endogenous interleukin-1 in the febrile response to localized inflammation in the rat

作     者：Cartmell, T Luheshi, GN Rothwell, NJ 

作者机构：Univ Manchester Sch Biol Sci Manchester M13 9PT Lancs England 

出 版 物：《JOURNAL OF PHYSIOLOGY-LONDON》 (生理学杂志)

年 卷 期：1999年第518卷第2期

页      面：585-594页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071003[理学-生理学] 

主　　题：体温/药物作用 脑/解剖学和组织学 脑化学/生理学 剂量效应关系 药物 发热/病理生理学 下丘脑/解剖学和组织学 下丘脑/药物作用 炎症/病理生理学 注射 脑室内 白细胞介素1/生理学 脂多糖类/药理学 微量注射 大鼠 Sprague-Dawley 受体 白细胞介素1/拮抗剂和抑制剂 动物 男(雄)性 大鼠 

摘      要：1. Interleukin (IL)-1 is a potent endogenous pyrogen which causes fever when injected into a number of brain sites. However, the brain sites at which endogenous IL-1 acts to influence body temperature remain equivocal. The aim of this study was to determine the effect of local administration of the interleukin-1 receptor antagonist (IL-1ra) into specific sites in the hypothalamus, and other brain regions known to contain receptors for IL-1, on the febrile response of rats to peripheral injection of lipopolysaccharide (LPS) into a subcutaneous air pouch (intrapouch, I.P.O.) that does not lead to LPS appearance in the circulation. 2. Injection of LPS (100 mu g kg(-1), I.P.O.) induced a rise in body temperature which commenced 1.5 h after injection and was maximal at 3 h (38.9 +/- 0.2 degrees C, compared with 37.0 +/- 0.1 degrees C at 0 h, n = 6, P 0.001). Intracerebrorventricular (I.C.V.) IL-1ra (500 mu g in 5 mu l) significantly attenuated LPS fever (IL-1ra, 37.7 +/- 0.2 degrees C;saline, 38.9 +/- 0.2 degrees C;n = 6, P 0.001). Unilateral microinjection of IL-1ra, (50 mu g in 0.5 mu l at 0 + 1 h) into the anterior hypothalamus (AH), paraventricular hypothalamic nucleus (PVH), peri-subfornical organ, subfornical organ (SPO) or hippocampus (dentate gyms and cA3 region) also significantly reduced the fever induced by LPS. 3. The same dose of IL-1ra had no effect on fever when administered into the ventromedial hypothalamus (VMH), organum vasculosum lamina terminalis (OVLT), CA1 field of the hippocampus, striatum or cortex. 4. These data indicate that the action of endogenous IL-1, in the brain during fever is site specific, acting at the AH, PVH, SFO and hippocampus, but not the VMH, OVLT and striatum or cortex.