Kox M, Pompe J C, Pickkers P, Hoedemaekers C W, van Vugt A B, van der Hoeven J G
Department of Intensive Care Medicine, Radboud University, Nijmegen Medical Centre, Geert Grooteplein 10, 6500 HB Nijmegen, The Netherlands.
Neurology. 2008 Feb 5;70(6):480-5. doi: 10.1212/01.wnl.0000279479.69502.3e.
Traumatic brain injury (TBI) is a leading cause of death and disability, especially in the younger population. In the acute phase after TBI, patients are more vulnerable to infection, associated with a decreased immune response in vitro. The cause of this immune paralysis is poorly understood. Apart from other neurologic dysfunction, TBI also results in an increase in vagal activity. Recently, the vagus nerve has been demonstrated to exert an anti-inflammatory effect, termed the cholinergic anti-inflammatory pathway. The anti-inflammatory effects of the vagus nerve are mediated by the alpha 7 nicotinic acetylcholine receptor present on macrophages and other cytokine-producing cells. From these observations, we hypothesize that the immune paralysis observed in patients with TBI may, at least in part, result from augmented vagal activity and subsequent sustained effects of the cholinergic anti-inflammatory pathway. This pathway may counteract systemic proinflammation caused by the release of endogenous compounds termed alarmins as a result of tissue trauma. However, sustained activity of this pathway may severely impair the body's ability to combat infection. Since the cholinergic anti-inflammatory pathway can be pharmacologically modulated in humans, it could represent a novel approach to prevent infections in patients with TBI.
创伤性脑损伤（TBI）是导致死亡和残疾的主要原因，尤其是在年轻人群中。在TBI后的急性期，患者更容易受到感染，这与体外免疫反应降低有关。这种免疫麻痹的原因尚不清楚。除了其他神经功能障碍外，TBI还会导致迷走神经活动增加。最近，迷走神经已被证明具有抗炎作用，称为胆碱能抗炎途径。迷走神经的抗炎作用是由巨噬细胞和其他产生细胞因子的细胞上存在的α7烟碱型乙酰胆碱受体介导的。基于这些观察结果，我们推测，TBI患者中观察到的免疫麻痹可能至少部分是由于迷走神经活动增强以及胆碱能抗炎途径的后续持续作用所致。该途径可能会抵消因组织创伤而释放内源性化合物警报素所引起的全身炎症反应。然而，该途径的持续活动可能会严重损害身体对抗感染的能力。由于胆碱能抗炎途径在人体中可以通过药物进行调节，因此它可能代表了一种预防TBI患者感染的新方法。
