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Beneficial Intervention of Experimental Colitis by Passive Cigarette Smoking Through the Modulation of Cytokines in Rats
  1. Joshua Ka-Shun Ko,
  2. Ngai-Fung Sham,
  3. Xin Guo,
  4. Chi-Hin Cho
  1. From the Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, China
  1. Address correspondence to: Joshua Ka-Shun Ko, PhD, Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 5 Sassoon Road, Hong Kong China. jksko{at}hkucc.hku.hk

Abstract

Background Epidemiologic observations have indicated that cigarette smoking 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 that the underlying mechanisms may involve immunoregulation of cytokines.

Methods Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Passive cigarette smoking by rats 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 therapeutic treatment of cyclosporin A or pentoxifylline, a tumor necrosis factor (TNF)-α 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-smoking rats. This was accompanied by attenuation of the elevated colonic myeloperoxidase and inducible nitric oxide synthase activities and leukotriene B4 level. Likewise, the augmentation in colonic levels of TNF-α, interleukin (IL)-1β, and IL-6 in colitis rats was also alleviated by passive cigarette smoking. In contrast, the deprivation of colonic IL-10 during colitis 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 passive cigarette smoking in experimental colitis involved immunoregulation of cytokines in colonic tissues.

Key Words:
  • ulcerative colitis
  • passive cigarette smoking
  • cytokines
  • immunomodulation
  • hapten

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