Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3.

Aims: Although excessive sympathetic activation in viral myocarditis and the protective effects of sympathetic inhibition with β-blockers are clear, the effects of enhancing vagal tone on viral myocarditis remain unclear. In several models, vagus nerve activation with the α7 nicotinic acetylcholine receptor (α7-nAChR) agonists has been demonstrated to ameliorate inflammation. This study was therefore designed to examine the effects of cholinergic stimulation with α7-nAChR agonist nicotine in a murine model of acute viral myocarditis.

Materials And Methods: BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine and methyllycaconitine (an α7-nAChR antagonist) were administered at doses of 0.4mg/kg and 0.8mg/kg three times per day for 7 or 14 consecutive days, respectively. The effects of nicotine and methyllycaconitine on survival rate, myocardial histopathological changes, cardiac function, cytokine levels, viral RNA, malondialdehyde, and superoxide dismutase contents were investigated.

Key Findings: Nicotine significantly increased survival rate of the infected mice, decreased myocardial inflammation, and improved the impairment of left ventricular function in murine coxsackievirus B3-induced myocarditis compared with methyllycaconitine. The proinflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17A were significantly decreased in the infected mice treated with nicotine compared with methyllycaconitine. Nicotine had no significant anti-oxidative and antiviral effects in coxsackievirus B3-infected mice.

Significance: The results indicate that cholinergic stimulation with nicotine significantly reduced the severity of viral myocarditis in mice. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with myocarditis.