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

Background Smoking, probably due to nicotine, has a bivalent effect on infl ammatory bower disease, ameliorating disease activity in ulcerative colitis and with a deleterious effect on Crohn's disease. The effect of nicotine p atches in ulcerative colitis is controversial. Aim To investigate the effect of chronic nicotine use in a rat model of col itis. Methods Colitis was induced in Sprague-Dawley rats by rectal administration of 30 mg trinitrobenzene sulphonic acid (TNBS) in 50% ethanol. Nicotine wa s dissolved in drinking water (2.5, 12.5, 25 and 250 mu g/ml), with rats dr inking ad libitum. Nicotine administration started 10 days prior to damage induction and had no effect on weight gain or daily food intake of rats. Ra ts were sacrificed 1 and 5 days after TNBS administration, their colons res ected, rinsed, weighed, damage assessed macroscopically (mm(2)) and microsc opically and tissue processed for myeloperoxidase (MPO) and nitric oxide sy nthase (NOS) activities, leukotriene B-4 (LTB4), prostaglandin E-2 (PGE(2)) 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 macroscop ic damage from 983 +/- 10 mm(2) on TNBS alone to 429 +/- 118 mm(2) on TNBS plus 12.5 mu g/ml of nicotine, and escalating to 1086 +/- 262 mm(2) on 250 mu g/ml of nicotine. Segmental weight declined significantly (from 2.4 +/- 0.2 to 1.65 +/- 0.20 g/10 cm), on 12.5 mu g/ml nicotine, as did MPO activit y (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 mu g/ml. Nicotine had no effect on NOS activity, PGE(2) generation and seru m IL-1 levels, but increased LTB4 generation. Conclusions Nicotine has a dose-dependent bivalent effect on TNBS-induced c olitis which is not due to reduction in IL-1 serum levels or PGE(2) generat ion, and is not NOS-mediated. Eur J Gastroenterol Hepatol 10:1013-1019 (C) 1998 Lippincott Williams & Wilkins.