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

BAOHUI JIA¹, YI CHEN², XIANGYANG LI³, MIN HUANG², MINGSHENG SHANG², NING LIU¹, LILI WU², ZHIJIE YAN²

¹Zhengzhou Railway Technology Vocation College, Zhengzhou 450052, Henan, China - ²Department of Critical Care Medicine, the Fourth Hospital Affiliated to Nanchang University, Nanchang 330003, Jiangxi, China - ³Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450052, Henan, China

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 (400μg/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-α and IL-1β) in mouse plasma corresponding to varying doses (40-400 μg/kg) of nicotine administered.

Results: Nicotine (400μg/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 (400μg/kg) significantly decreased the serum levels of TNF-α (531.79 ± 8.14 vs. 731.11 ± 42.56 in CLP group; P<0.01) and IL-1β (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.

Keywords: Nicotine, Cholinergic anti-inflammatory pathway, Sepsis, Tumor necrosis factor, Interleukine-1β.