Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
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DOI：
10.1038/35013070
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发表时间：
2000-05-25
期刊：
影响因子：
64.8
通讯作者：
Tracey, KJ
中科院分区：
文献类型：
--
作者：
Borovikova, LV;Ivanova, S;Tracey, KJ
脊椎动物在感染或损伤期间通过平衡促炎和抗炎途径的活性来实现内部稳态。所有革兰氏阴性细菌都会产生内毒素（脂多糖），它会激活巨噬细胞释放可能致命的细胞因子(1-4)。中枢神经系统通过体液机制调节对内毒素的全身炎症反应(5-8)。内毒素或细胞因子激活传入迷走神经纤维会刺激下丘脑-垂体-肾上腺抗炎反应(9-11)。然而，人们对传出迷走神经信号在调节炎症中的作用知之甚少。在这里，我们描述了一种以前未被认识的副交感抗炎途径，大脑通过该途径调节对内毒素的全身炎症反应。在脂多糖刺激的人巨噬细胞培养物中，乙酰胆碱是主要的迷走神经递质，可显着减弱细胞因子（肿瘤坏死因子（TNF）、白细胞介素（IL）-1β、IL-6和IL-18）的释放，但不会减弱抗炎细胞因子IL-10的释放。在大鼠致死性内毒素血症期间，直接电刺激体内周围迷走神经可抑制肝脏中 TNF 的合成，减弱血清 TNF 峰值含量，并防止休克的发生。
Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal(1-4). The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms(5-8). Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses(9-11). However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1 beta, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.