Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis

Background. Smoking, probably due to nicotine, has a bivalent effect on inflammatory bowel disease, ameliorating disease activity in ulcerative colitis and with a deleterious effect on Crohn's disease. The effect of nicotine patches in ulcerative colitis is controversial. Aim. To investigate the effect of chronic nicotine use in a rat model of colitis. Methods. Colitis was induced in Sprague-Dawley rats by rectal administration of 30 mg trinitrobenzene sulphonic acid (TNBS) in 50% ethanol. Nicotine was dissolved in drinking water (2.5, 12.5, 25 and 250 μg/ml), with rats drinking ad libitum. Nicotine administration started 10 days prior to damage induction and had no effect on weight gain or daily food intake of rats. Rats were sacrificed 1 and 5 days after TNBS administration, their colons resected, rinsed, weighed, damage assessed macroscopically (mm²) and microscopically and tissue processed for myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities, leukotriene B₄ (LTB₄), prostaglandin E₂ (PGE₂) generation and interleukin-1 (IL-1) serum levels. Results. Nicotine, by itself, caused no damage to the colon. Nicotine had a dose-dependent bivalent effect on colitis, significantly reducing macroscopic damage from 983 ± 10 mm² on TNBS alone to 429 ± 118 mm² on TNBS plus 12.5 μg/ml of nicotine, and escalating to 1086 ± 262 mm² on 250 μg/ml of nicotine. Segmental weight declined significantly (from 2.4 ± 0.2 to 1.65 ± 0.20 g/10 cm), on 125 μg/ml nicotine, as did MPO activity (from 3.2 ± 0.4 to 0.7 ± 0.1 units/g). All these parameters returned to the levels of TNBS alone when the dose of nicotine was increased to 250 μg/ml. Nicotine had no effect on NOS activity, PGE₂ generation and serum IL-1 levels, but increased LT₄ generation. Conclusions. Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE₂ generation, and is not NOS-mediated.