Beneficial intervention of experimental colitis by passive cigarette smoking through the modulation of cytokines in rats

Background: Epidemiologic observations have indicated that cigarette smokin g decreases the risk of ulcerative colitis, but the modes of action remain anonymous. The present study aimed to investigate the beneficial effects of passive cigarette smoking using an animal colitis model. We hypothesized t hat the underlying mechanisms may involve immunoregulation of cytokines. Methods: Experimental colitis was induced in rats by enema administration o f 2,4-dinitrobenzene sulfonic acid (DNBS). Passive cigarette smoking by rat s was performed for 1 hour once daily, from 3 days before DNBS enema until they were sacrificed on day 8, Other groups of DNBS-treated rats received t herapeutic treatment of cyclosporin A or pentoxifylline, a tumor necrosis f actor (TNF)-alpha inhibitor. Macroscopic and histologic damage were graded, and the colonic levels of different cytokines and the levels/activities of parameters related to neutrophil activation were also measured. Results: DNBS-induced colonic damage was improved in passive cigarette-smok ing rats. This was accompanied by attenuation of the elevated colonic myelo peroxidase and inducible nitric oxide synthase activities and leukotriene B -4 level. Likewise, the augmentation in colonic levels of TNF-alpha, interl eukin (IL)-1 beta, and IL-6 in colitis rats was also alleviated by passive cigarette smoking. In contrast, the deprivation of colonic IL-10 during col itis was preserved in cigarette-smoking rats. These effects were similarly accomplished by pentoxifylline and, to some degree, by cyclosporin A. Conclusions: The results support the idea that the beneficial effects of pa ssive cigarette smoking in experimental colitis involved immunoregulation o f cytokines in colonic tissues.