Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3.
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.
Department of Pediatrics, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Ge
G
Li-Sha
Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Zhao
Z
Jing-Lin
Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Chen
C
Guang-Yi
Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Liu
L
Li
Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Zhou
Z
De-Pu
Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Li
L
Yue-Chun
D000818:Animals; D029822:Enterovirus B, Human / Q000187:drug effects*; D004769:Enterovirus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D007249:Inflammation / Q000378:metabolism / Q000821:virology; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D009206:Myocardium / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014777:Virus Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology
D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine