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. Our objective was 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 given daily intraperiotonal (i.p.) injections of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (1 mg/kg) 45 min before subcutaneous (s.c.) injections in the neck skin with nicotine (0.8 mg/kg), or treated with the same amount of saline i.p. and nicotine s.c., or with mecamylamine and saline. Control rats received i.p. and s.c. injections of saline only. Periodontal bone loss was assessed when the ligatures had been in place for 3 weeks. Two hours before decapitation, all rats received lipopolysaccharide (LPS; 100 microg/kg, i.p.) to induce a robust immune and stress response.

Compared with saline/saline-treated control rats, 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 (TNF-alpha), transforming growth factor 1beta (TGF-1beta) and interleukin-10 (IL-10). Mecamylamine pretreatment of nicotine-treated rats abrogated the increased periodontal bone loss and the LPS-induced TNF-alpha decrease, but had no significant effects on the levels of TGF-1beta and IL-10, or the stress hormone corticosterone.

The results indicate that nicotine enhances susceptibility to periodontitis via nAChRs, which may act via suppressing protective immune responses through the cholinergic anti-inflammatory pathway.