Subdiaphragmatic vagotomy blocks interleukin-1β-induced fever but does not reduce IL-1β levels in the circulation
Subdiaphragmatic vagotomy blocks interleukin-1β-induced fever but does not reduce IL-1β levels in the circulation
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DOI：
10.1016/s1566-0702(00)00222-8
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发表时间：
2000-12-20
影响因子：
2.7
通讯作者：
Watkins, LR
中科院分区：
文献类型：
--
作者：
Gaykema, RPA;Goehler, LE;Watkins, LR
外周白介素 1 β 与发烧反应的启动有关，但其影响大脑功能的途径仍不清楚。据报道，腹腔注射白细胞介素 1 β 后，腹部迷走神经切片可抑制发烧，这表明迷走神经传入参与向大脑发出信号，以对白细胞介素 1 β 产生发烧反应。然而，膈下迷走神经切断术的抑制作用可能是由于药代动力学的改变，使得腹膜内注射的细胞因子无法以足够的量到达全身循环以通过血源性信号传导激活大脑。我们在腹腔注射 1 杯/kg 人重组白介素 1 β 后，测量了迷走神经切断和假手术大鼠的发热和血浆白细胞介素 1 β 水平，以确定迷走神经切断术是否会降低腹腔注射后的发热和循环白细胞介素 1 β 水平。在单独的酶联免疫吸附测定中测量了人重组和内源性大鼠白介素-1β的血浆水平。虽然在迷走神经切断和假手术动物中腹膜内给予人重组白细胞介素-1β可类似地升高该细胞因子的血浆水平，但只有假手术大鼠出现发烧反应。任何治疗均未改变大鼠内源性白介素-1β的血浆水平。这些结果表明，膈下迷走神经切断术后腹膜内白细胞介素 1 β 诱导的发热的阻断不能通过体循环中白细胞介素 1 β 水平的改变来解释。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Peripheral interleukin-1 beta has been implicated in the initiation of fever responses, yet the pathways by which it influences brain function are still unclear. Sectioning the abdominal vagus has been reported to inhibit fever after intraperitoneal administration of interleukin-1 beta, suggesting that vagal afferents participate in signaling the brain to mount a fever response to interleukin-1 beta. However, the inhibitory effect of subdiaphragmatic vagotomy could be due to alterations in pharmacokinetics such that the intraperitoneally injected cytokine does not reach the general circulation in sufficient quantities to activate the brain via blood-borne signaling. We measured both fever and plasma levels of interleukin-1 beta in vagotomized and sham-operated rats after intraperitoneal administration of 1 mug/kg human recombinant interleukin-1 beta to determine whether vagotomy reduces fever and levels of circulating interleukin-1 beta after intraperitoneal injection. Plasma levels of human recombinant and endogenous rat interleukin-1 beta were measured in separate enzyme-linked immunosorbent assays. While intraperitoneal administration of human recombinant interleukin-1 beta elevated plasma levels of this cytokine similarly in vagotomized and sham-operated animals, only sham-operated rats responded with fever. Plasma levels of endogenous rat interleukin-1 beta were unchanged by any treatment. These results demonstrate that the blockade of intraperitoneal interleukin-1 beta -induced fever after subdiaphragmatic vagotomy cannot be accounted for by alterations of interleukin-1 beta levels in the general circulation. (C) 2000 Elsevier Science B.V. All rights reserved.