Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.

PloS one

PubMedID: 25396421

Cheng Z, Li-Sha G, Jing-Lin Z, Wen-Wu Z, Xue-Si C, Xing-Xing C, Yue-Chun L. Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis. PLoS ONE. 2014;9(11):e112719.
BACKGROUND
Activation of the cholinergic anti-inflammatory pathway, which relies on the a7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis.

METHODOLOGY/PRINCIPAL FINDINGS
In a coxsackievirus B3 murine myocarditis model (Balb/c), nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-a and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-a and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group.

CONCLUSIONS/SIGNIFICANCE
These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a a7nAchR agonist and methyllycaconitine is a a7nAchR antagonist, we conclude that a7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-a and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking a7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-a and IL-6, aggravating viral myocarditis.