Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

Sci Rep. 2015 Oct 28;5:15895. doi: 10.1038/srep15895.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enterovirus B, Human / drug effects*
  • Enterovirus Infections / drug therapy*
  • Enterovirus Infections / metabolism
  • Enterovirus Infections / virology
  • Inflammation / metabolism
  • Inflammation / virology
  • Interleukin-17 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis / drug therapy*
  • Myocarditis / metabolism
  • Myocarditis / virology*
  • Myocardium / metabolism
  • Nicotine / pharmacology*
  • Protective Agents / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Virus Diseases / drug therapy*
  • Virus Diseases / metabolism
  • Virus Diseases / virology

Substances

  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-6
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • Nicotine