Interleukin-6 and leptin mediate lipopolysaccharide-induced fever and sickness behavior
Interleukin-6 and leptin mediate lipopolysaccharide-induced fever and sickness behavior
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DOI：
10.1016/j.physbeh.2006.05.016
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发表时间：
2006-09-30
影响因子：
2.9
通讯作者：
Laburn, Helen P.
中科院分区：
文献类型：
--
作者：
Harden, Lois M.;du Plessis, Irne;Laburn, Helen P.
由活化的巨噬细胞和单核细胞响应于脂多糖（LPS）的施用而合成的促炎细胞因子白介素（IL）-1 β、IL-6和肿瘤坏死因子-α（TNF-α）被认为是发热和疾病行为的重要介质。我们给予大鼠特异性抗血清TNF-α，IL-1 β，IL-6和瘦素，以确定外周释放的细胞因子参与LPS诱导的发热和疾病行为，测量自愿车轮运行和食物摄入的抑制。将因其在转轮上自发奔跑的倾向而选择的雄性Sprague-Dawley大鼠（类似于200 g）用盐酸氯胺酮（80 mg/kg i.m.）和甲苯噻嗪（4 mg/kg i.m.）并在腹腔内植入温度敏感的无线电遥测仪。向大鼠腹膜内注射针对以下之一的抗大鼠血清：TNF-α、IL-10、IL-6或瘦素，或免疫前绵羊血清，随后皮下注射LPS（250 μ g/kg）或无菌盐水。与生理盐水反应相比，脂多糖给药诱导了类似于1.3（0.2）℃的持续类似于10 h的发热，并使自主跑步减少了93（8.6）%，食物摄入减少了51（21.3）%（ANOVA，P < 0.05）。注射抗IL-6血清或抗Leptin血清可消除LPS引起的发热，抗TNF-α血清仅影响发热早期，抗IL-1 β血清对发热无影响（ANOVA，P < 0.05）。抗IL-6血清可减轻LPS对大鼠自主运动和摄食量的抑制作用，而抗Leptin血清可完全消除LPS对大鼠摄食量的抑制作用（ANOVA，P < 0.05）。注射抗TNF-α或抗IL-1 β血清对LPS诱导的病态行为没有影响。因此，外周释放的IL-6和瘦素似乎在调节LPS诱导的发热和疾病行为中很重要。(c)2006年爱思唯尔公司All rights reserved.
Pro-inflammatory cytokines, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) synthesized by activated macrophages and monocytes in response to administration of lipopoysaccharide (LPS), are considered important mediators of fever and sickness behavior. We administered rat-specific antisera for TNF-alpha, IL-1 beta, IL-6 and leptin, to determine the involvement of peripherally released cytokines in LPS-induced fever and sickness behavior, measured as suppression of voluntary wheel-running and food intake. Male Sprague-Dawley rats (similar to 200 g) selected for their predisposition to spontaneously run on running wheels were anaesthetized with a combination of ketamine hydrochloride (80 mg/kg i.m.) and xylazine (4 mg/kg i.m.) and implanted intra-abdominally with temperature-sensitive radiotelemeters. Rats were injected intraperitoneally with anti-rat sera to one of the following, TNF-alpha, IL-10, IL-6 or leptin or with pre-immune sheep serum, followed by a subcutaneous injection of either LPS (250 mu g/kg) or sterile saline. Lipopolysaccharide administration induced a similar to 1.3 (0.2) degrees C fever lasting similar to 10 h and reduced voluntary running by 93 (8.6)% and food intake by 51 (21.3)% compared to the saline response (ANOVA, P < 0.05). Injection of anti-IL-6 serum or anti-leptin serum abolished the LPS-induced fever, anti-TNF-alpha serum affected only the early phase of fever and anti-IL-1 beta serum had no effect on fever (ANOVA, P < 0.05). LPS-induced suppression of voluntary running and food intake were attenuated in rats receiving anti-IL-6 serum, while the decrease in food intake was totally abolished in rats receiving anti-leptin serum (ANOVA, P < 0.05). Injection of anti-TNF-alpha or anti-IL-1 beta serum had no effect on LPS-induced sickness behavior. Peripherally released IL-6 and leptin therefore appear to be important in regulating LPS-induced fever and sickness behavior. (c) 2006 Elsevier Inc. All rights reserved.