Abstract
The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.
Highlights
Significant reductions in the cardiac pathological scores, including infiltration and necrosis were achieved in the groups with high- and medium-dose nicotine treatments compared with the myocarditis group (Fig. 1, Table 1)
We examined the therapeutic effects of nicotine in viral myocarditis
The high- and medium-dose nicotine treatments ameliorated the myocardial lesions and improved the impairments of left ventricular function of mice infected with coxsackievirus B3 (CVB3)
Summary
Innate immune cytokines such as TNF-α, IL-1β, and IL-6 are essential for the development of acute viral-induced myocarditis. Leib et al reported that nicotine, an alpha[7] nAChR agonists, decreased heart inflammation in a murine autoimmune myocarditis model[19]. We have found that activation of the cholinergic anti-inflammatory pathway reduced inflammation in viral myocarditis[20]. The dose-dependent effects of alpha[7] nAChR agonists in acute murine viral-induced myocarditis and on cytokine production are not well known. The present study was performed to examine the therapeutic effects of different doses of the selective alpha[7] nAChR agonist nicotine in a murine model of viral myocarditis induced by CVB3 infection
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