title: Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pediatrics, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Ge
authors: G
authors: Li-Sha
authors: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Zhao
authors: Z
authors: Jing-Lin
authors: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Liu
authors: L
authors: Li
authors: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Chen
authors: C
authors: Guang-Yi
authors: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Li
authors: L
authors: Xiao-Wei
authors: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: liyuechun1980@sina.com.
authors: Li
authors: L
authors: Yue-Chun
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000378:metabolism*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004770:Enterovirus / Q000187:drug effects / Q000378:metabolism*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine
keywords: Cytokines; Myocarditis; α7 nicotinic acetylcholine receptor