Czura Christopher J, Friedman Steven G, Tracey Kevin J
Laboratory of Biomedical Science, North Shore-LIJ Research Institute, Manhasset, NY 11030, USA.
J Endotoxin Res. 2003;9(6):409-13. doi: 10.1179/096805103225002755.
The innate immune system is activated by infection and injury to release pro-inflammatory cytokines, which activate macrophages and neutrophils and modulate specific cellular responses. The magnitude of the cytokine response is critical, because a deficient response may result in secondary infections, while an excessive response may be more injurious than the original insult. We recently described a neural pathway, termed the "cholinergic anti-inflammatory pathway", that reflexively monitors and adjusts the inflammatory response by inhibiting pro-inflammatory cytokine synthesis. Efferent signals in the vagus nerve provide a direct mechanism for neural regulation of the immune response that is rapid, localized, and integrated. Vagus nerve stimulation inhibits the release of TNF, HMGB1, and other cytokines, and protects against endotoxemia and ischemia-reperfusion injury. This newly identified physiological mechanism of maintaining immunological homeostasis suggests that novel therapeutics may effectively modulate inflammatory responses by activating the cholinergic anti-inflammatory pathway.
先天性免疫系统通过感染和损伤被激活，释放促炎细胞因子，这些因子激活巨噬细胞和中性粒细胞并调节特定的细胞反应。细胞因子反应的强度至关重要，因为反应不足可能导致继发感染，而反应过度可能比最初的损伤更具危害性。我们最近描述了一条神经通路，称为“胆碱能抗炎通路”，它通过抑制促炎细胞因子的合成来反射性地监测和调节炎症反应。迷走神经中的传出信号为免疫反应的神经调节提供了一种直接机制，这种机制快速、局部且整合性强。迷走神经刺激可抑制肿瘤坏死因子、高迁移率族蛋白B1和其他细胞因子的释放，并预防内毒素血症和缺血再灌注损伤。这种新发现的维持免疫稳态的生理机制表明，新型疗法可能通过激活胆碱能抗炎通路有效地调节炎症反应。
