PROTECTIVE EFFECTS OF NICOTINE AGAINST SEPSIS IN MICE AFTER A CLP VIA ACTIVATING CHOLINERGIC ANTI-INFLAMMATORY PATHWAY

Objective: To investigate the effects of nicotine on sepsis in mice. Methods: Sepsis was induced in female Kunming mice with cecal ligation and puncture operation (CLP). The experiment group were administered nicotine (400 mu g/kg) 30 minutes before and three times daily for 3 days after sepsis induction. Survival of mice was observed up to 7 days after CLP in a total of 65 mice. In a separate experiment, the severity of the sepsis was evaluated and lung and liver histopathological examinations were performed (n=18). In the third experiment (n=120), we examined the temporal levels of proinflammatory cytokines (TNF-alpha and IL-1 beta) in mouse plasma corresponding to varying doses (40-400 mu g/kg) of nicotine administered. Results: Nicotine (400 mu g/kg) significantly increased the survival rate of CLP mice compared to those of the control group (56.7% vs. 20%; P<0.01). It could attenuate sepsis severity (15.00 +/- 3.58 in experiment group vs. 21.00 +/- 2.37 in CLP group; P<0.05) and decrease the lung wet/dry weight ratio (2.30 +/- 1.03 vs. 2.71 +/- 1.58 in CLP group; P<0.05). It could also ameliorate hepatic and lung damage. Six hours after administration, nicotine (400 mu g/kg) significantly decreased the serum levels of TNF-alpha (531.79 +/- 8.14 vs. 731.11 +/- 42.56 in CLP group; P<0.01) and IL-1 beta (245.19 +/- 35.03 vs. 556.12 +/- 7.08 in CLP group; P<0.01). Conclusions: Nicotine has protective effects against sepsis in mice, and it could be attributed to its activation of cholinergic anti-inflammatory pathway to inhibit the production of inflammatory cytokines.