The contribution of the vagus nerve in interleukin-1beta-induced fever is dependent on dose.
The contribution of the vagus nerve in interleukin-1beta-induced fever is dependent on dose.
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DOI：
10.1152/ajpregu.2001.280.4.r929
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发表时间：
2001-04
期刊：
影响因子：
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通讯作者：
M. K. Hansen;Kevin A. O’Connor;L. Goehler;L. Goehler;L. Watkins;S. Maier
中科院分区：
文献类型：
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作者：
M. K. Hansen;Kevin A. O’Connor;L. Goehler;L. Goehler;L. Watkins;S. Maier
已有研究表明，促炎症细胞因子除了通过血液传播途径外，还通过一条神经通路与大脑进行通讯，该通路涉及到白介素1β(IL-1β)激活迷走神经传入。在支持方面，隔膜下迷走神经切断术阻止了IL-1β诱导的大脑中介反应，如发烧。然而，据报道，迷走神经切断术也没有效果。在低剂量的细胞因子作用下，神经信号尤其重要，因为局部作用可能会发生，但只有非常少量的细胞因子会变成全身的。在这里，我们检测了腹腔注射三种剂量的重组人IL-1β(rh-IL-1β)后的核心体温。隔下迷走神经切断术完全阻断0.1微克/公斤所致发热，仅部分阻断0.5微克/公斤所致发热，对1.0微克/公斤重组人IL-1β所致发热无明显影响。直到0.5微克/公斤剂量时，血中rh-IL-1β的水平才会高于正常的内源性IL-β的基础水平，而在此剂量之前，脑垂体中也没有诱导出IL-1β。这些结果表明，小剂量的IL-1β通过迷走神经途径引起发热，这一剂量可能解释了文献中的一些差异。
It has been suggested that proinflammatory cytokines communicate to the brain via a neural pathway involving activation of vagal afferents by interleukin-1beta (IL-1beta), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy blocks IL-1beta-induced, brain-mediated responses such as fever. However, vagotomy has also been reported to be ineffective. Neural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities of cytokine would become systemic. Here, we examined core body temperature after intraperitoneal injections of three doses of recombinat human IL-1beta (rh-IL-1beta). Subdiaphragmatic vagotomy completely blocked the fever produced by 0.1 microg/kg, only partially blocked the fever produced by 0.5 microg/kg, and had no effect at all on the fever that followed 1.0 microg/kg rh-IL-1beta. Blood levels of rh-IL-1beta did not become greater than normal basal levels of endogenous rat IL-beta until the 0.5-microg/kg dose nor was IL-1beta induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1beta induce fever via a vagal route and that dose may account for some of the discrepancies in the literature.