Nicotinic acetylcholine receptor activation mediates nicotine-induced enhancement of experimental periodontitis

Smokers have an increased risk of developing periodontitis as well as showing more rapid progression and resistance to treatment of the disease, but the biological mechanisms are poorly understood. This study was designed to investigate putative biological mechanisms by which nicotine may enhance the susceptibility and thus the course of periodontitis in an animal model. Ligature-induced periodontitis was applied in periodontitis-susceptible Fischer 344 rats. The animals were either given daily intraperitoneal injections of the nicotinic acetylcholine receptor antagonist mecamylamine (1 mg/kg) 45 min before subcutaneous injections in the neck skin of nicotine (0.8 mg/kg), or treated with the same amount of saline intraperitoneally and nicotine subcutaneously, or treated with mecamylamine and saline. Control animals received intraperitoneal and subcutaneous injections of saline only. Periodontal bone loss was assessed when the ligatures had been in place for 3 wk. Two hours before decapitation, all rats received lipopolysaccharide (LPS; 100 mu g/kg, intraperitoneally) to induce a robust immune and stress response. Compared with saline/saline-treated control animals, saline/nicotine-treated rats developed significantly more periodontal bone loss, and LPS provoked a significantly smaller increase in circulating levels of the cytokines tumour necrosis factor-alpha, transforming growth factor-1 beta and interleukin-10. Mecamylamine pretreatment of nicotine-treated rats abrogated the increased periodontal bone loss and the LPS-induced decrease in tumour necrosis factor-alpha, but had no significant effects on the levels of transforming growth factor-1 beta and interleukin-10, or the stress hormone corticosterone. The results indicate that nicotine enhances the susceptibility to periodontitis via nicotinic acetylcholine receptors, which may act by suppressing protective immune responses through the cholinergic anti-inflammatory pathway.