The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals. This effect was mediated by acetylcholine (ACh) stimulation of nicotinic receptors on splenic macrophages. Hence, the circuit was dubbed the “cholinergic anti-inflammatory pathway”. Subsequent work identified the α7 nicotinic ACh receptor (α7nAChR) as the crucial target for attenuation of pro-inflammatory cytokine release from macrophages and dendritic cells. Further investigation made the important discovery that cholinergic T cells within the spleen and not cholinergic nerve cells were the source of ACh that stimulated α7 receptors on splenic macrophages. Given the important role that inflammation plays in numerous disease processes, cholinergic anti-inflammatory mechanisms are under intensive investigation from a basic science perspective and in translational studies of animal models of diseases such as inflammatory bowel disease and rheumatoid arthritis. This basic work has already fostered several clinical trials examining the efficacy of VNS and cholinergic therapeutics in human inflammatory diseases. This review provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response and relevant pharmacology of drugs acting at the α7nAChR.

神经系统和免疫系统在人体中分布广泛且重叠，这些无处不在的系统之间的相互作用是神经免疫学领域的核心。在过去的二十年中，我们对神经解剖，细胞和分子机制的理解有了爆炸性增长，这些机制通过自主神经系统介导免疫功能的中央调节。在该领域中生长的主要催化剂是发现迷走神经刺激（VNS）引起实验动物内毒素引起的全身炎症反应的显着减弱。这种作用是通过乙酰胆碱（ACh）刺激脾巨噬细胞上的烟碱样受体而介导的。因此，该回路被称为“胆碱能抗炎途径”。随后的工作确定了α7烟碱型ACh受体（α7nAChR）是减轻巨噬细胞和树突状细胞促炎性细胞因子释放的关键靶标。进一步的研究得出了重要发现，即脾脏中的胆碱能T细胞而非胆碱能神经细胞是刺激脾脏巨噬细胞上的α7受体的ACh的来源。鉴于炎症在许多疾病过程中起着重要作用，从基础科学的角度以及在对诸如炎症性肠病和类风湿性关节炎等疾病的动物模型的转化研究中，对胆碱能抗炎机制进行了深入研究。这项基础工作已经促进了几项临床试验，以检验VNS和胆碱能疗法在人类炎症性疾病中的功效。