Dual effect of chronic nicotine administration: augmentation of jejunitis and amelioration of colitis induced by iodoacetamide in rats

Smoking has a dichotomous effect on inflammatory bowel disease, amelioratin g disease activity in ulcerative colitis but having a deleterious effect on Crohn's disease. This effect is thought to be due to nicotine. We investig ated the effect of chronic nicotine administration on the small and large b owel in iodoacetamide-induced jejunitis and colitis. Jejunitis was induced in Sprague-Dawley rats by intrajejunal administration of 0.1 ml 2% iodoacet amide and colitis by intrarectal administration of 0.1 ml 3% iodoacetamide. Nicotine was dissolved in drinking water (12.5 or 250 mug/ml), rats drinki ng ad libitum. Nicotine administration started 10 days prior to damage indu ction and throughout the experiment and had no effect on weight gain or dai ly food intake of rats. Rats were killed 5 days after iodoacetamide-induced colitis and 7 days after induction of jejunitis. The jejunum and colon wer e resected, rinsed, weighed, damage assessed macroscopically and microscopi cally and tissue processed for myeloperoxidase and nitric oxide synthase (N OS) activities and prostaglandin E-2 (PGE(2)) generation. Effects of nicoti ne on gut microcirculation were also assessed. Nicotine by itself caused no damage to the colon. Nicotine had a dichotomous effect on jejunitis and co litis. At a dose of 12.5 mug/ml nicotine improved the macroscopic damage of colitis from 252+/-66 to 70+/-31 mm(2), and segmental weight also declined significantly in the colon (from 1.7+/-0.2 to 1.2+/-0.1 g/10 cm). In contr ast, the same dose of nicotine had a deleterious effect on iodoacetamide-in duced jejunitis, increasing the macroscopic damage from 368+/-38 to 460+/-9 7 mm(2) in rats treated with injury escalating to 970+/-147 in rats treated with 250 mug/ml nicotine. Nicotine treatment also significantly increased jejunal segmental weight. By itself nicotine did not change NOS activity or PGE(2) generation compared to control rats, but it enhanced microcirculati on in the colon, whereas in the jejunum nicotine decreased PGE(2) generatio n and increased NOS activity but not jejunal microcirculation. Nicotine has opposite effects on iodoacetamide-induced colitis and jejunitis, which may be partly explained by decreased PGE(2) generation and increased NOS activ ity in the jejunum and an increase in the colonic microcirculation.