Cholinergic modulation of the immune system - A novel therapeutic target for myocardial inflammation.

The immune system and the nervous system depend on each other for their fine tuning and working, thus cooperating to maintain physiological homeostasis and prevent infections. The cholinergic system regulates the mobilization, differentiation, secretion, and antigen presentation of adaptive and innate immune cells mainly through α7 nicotinic acetylcholine receptors (α7nAChRs). The neuro-immune interactions are established and maintained by the following mechanisms: colocalization of immune and neuronal cells at defined anatomical sites, expression of the non-neuronal cholinergic system by immune cells, and the acetylcholine receptor-mediated activation of intracellular signaling pathways. Based on these immunological mechanisms, the protective effects of cholinergic system in animal models of diseases were summarized in this paper, such as myocardial infarction/ischemia-reperfusion, viral myocarditis, and endotoxin-induced myocardial damage. In addition to maintaining hemodynamic stability and improving the energy metabolism of the heart, both non-neuronal acetylcholine and neuronal acetylcholine in the heart can alleviate myocardial inflammation and remodeling to exert a significant cardioprotective effect. The new findings on the role of cholinergic agonists and vagus nerve stimulation in immune regulation are updated, so as to develop improved approaches to treat inflammatory heart disease.