Central substance P NK1 receptors are involved in fever induced by LPS but not by IL-1β and CCL3/MIP-1α in rats
Central substance P NK1 receptors are involved in fever induced by LPS but not by IL-1β and CCL3/MIP-1α in rats
复制标题
DOI：
10.1016/j.brainres.2011.02.001
复制
发表时间：
2011-04-12
期刊：
影响因子：
2.9
通讯作者：
Zampronio, A. R.
中科院分区：
文献类型：
--
作者：
Reis, R. C.;Brito, H. O.;Zampronio, A. R.
P物质（SP）是一种神经肽，可以通过激活NK 1受体（NK 1 R）来调节炎症介质的释放。一些研究还表明SP参与脂多糖（LPS）诱导的发热。然而，这种神经肽对发热期间激活的通路的确切贡献尚不清楚。在这项研究中，我们研究了选择性NK 1 R拮抗剂SR 140333 B对LPS和细胞因子诱导的发热反应的影响。我们的结果表明，全身注射SR 140333 B在能够减少皮肤中SP诱导的蛋白外渗的剂量下不会改变LPS诱导的发热。另一方面，脑室内给予5 R140333 B显着降低了外周注射LPS引起的发热。这些数据强调了一个重要的作用，SP在中枢神经系统中的LPS的发热反应，并加强了这一事实，即脑室注射SP也诱导发热在剂量依赖性的方式在卡托普利治疗的大鼠。考虑到发热反应可能由几种内源性热原（其中包括白细胞介素（IL）-1 β和巨噬细胞炎性蛋白-1 α（CCL 3/MIP-1 α））的产生引起，我们还检查了SR 140333 B对这些细胞因子诱导的发热的影响，这些细胞因子分别通过伊兰定依赖性和非依赖性机制发挥作用。令人惊讶的是，SR 140333 B没有改变对IL-1 β或CCL 3/MIP-1 α的发热反应。总之，这些数据表明，SP的中枢作用是必不可少的LPS-，但不是IL-1 β或CCL 3/MIP-1 α-诱导的发热。(C)2011 Elsevier B. V.保留所有权利。
Substance P (SP) is a neuropeptide that can modulate inflammatory mediator release through activation of NK1 receptors (NK1R). Some studies have also suggested the involvement of SP in lipopolysaccharide (LPS)-induced fever. However, the precise contribution of this neuropeptide to the pathways activated during fever is unknown. In this study we investigated the effect of a selective NK1R antagonist, SR140333B, on the febrile response induced by LPS and cytokines. Our results show that the systemic injection of SR140333B did not modify the fever induced by LPS at a dose that is able to reduce protein extravasation induced by SP in the skin. On the other hand, intracerebroventricular administration of 5R140333B significantly reduced the fever induced by peripheral injection of LPS. These data emphasize an important role for SP in the central nervous system during the febrile response to LPS, and are reinforced by the fact that intracerebroventricular injection of SP also induced fever in a dose-dependent manner in captopril-treated rats. Considering that the febrile response can result from the generation of several endogenous pyrogens, among them interleukin (IL)-1 beta and macrophage inflammatory protein-1 alpha (CCL3/MIP-1 alpha), we also examined the effect of SR140333B on the fever induced by these cytokines which act through prostaglandin-dependent and independent mechanisms, respectively. Surprisingly, SR140333B did not modify the febrile response to IL-1 beta or CCL3/MIP-1 alpha. Altogether these data suggest that the central action of SP is essential for LPS-, but not for IL-1 beta- or CCL3/MIP-1 alpha-induced fever. (C) 2011 Elsevier B.V. All rights reserved.