Brito Haissa Oliveira, Barbosa Felipe L, Reis Renata Cristiane Dos, Fraga Daniel, Borges Beatriz S, Franco Celia R C, Zampronio Aleksander Roberto
Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
Department of Cell Biology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
J Neuroimmunol. 2016 Apr 15;293:1-7. doi: 10.1016/j.jneuroim.2016.01.016. Epub 2016 Jan 27.
Substance P (SP) is involved in fever that is induced by lipopolysaccharide (LPS) but not by interleukin-1β or macrophage inflammatory protein-1α. Intracerebroventricular (i.c.v.) administration of the neurokinin-1 (NK1) receptor antagonist SR140333B in rats reduced fever that was induced by an i.c.v. injection of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), corticotropin-releasing factor (CRF), endothelin-1 (ET-1), and morphine (MOR). Furthermore, an i.c.v. injection of SP induced a febrile response that was inhibited by indomethacin concomitant with an increase in PGE2 levels in cerebrospinal fluid. Lipopolysaccharide and PGE2 caused higher expression and internalization of NK1 receptors in the hypothalamus which were prevented by SR140333B. These data suggest that SP is an important mediator of fever, in which it induces a prostaglandin-dependent response and is released after TNF-α, IL-6, PGE2, CRF, endogenous opioids, and ET-1.
P物质（SP）参与脂多糖（LPS）诱导的发热，但不参与白细胞介素-1β或巨噬细胞炎性蛋白-1α诱导的发热。给大鼠脑室内（i.c.v.）注射神经激肽-1（NK1）受体拮抗剂SR140333B可减轻由脑室内注射肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、前列腺素E2（PGE2）、促肾上腺皮质激素释放因子（CRF）、内皮素-1（ET-1）和吗啡（MOR）诱导的发热。此外，脑室内注射SP可诱导发热反应，吲哚美辛可抑制该反应，同时脑脊液中PGE2水平升高。脂多糖和PGE2导致下丘脑NK1受体表达增加和内化，而SR140333B可阻止这种情况。这些数据表明，SP是发热的重要介质，它诱导前列腺素依赖性反应，并在TNF-α、IL-6、PGE2、CRF、内源性阿片类物质和ET-1之后释放。
