Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats

Background & Aims: Cigarette smoking is associated with inflammatory bower diseases (IBDs), particularly Crohn's disease, in humans. The aim of this s tudy was to examine whether passive cigarette smoking aggravates experiment al IBD in rats and to clarify the underlying mechanisms. Methods: Rats were exposed to cigarette smoke (CS) for 1 hour once daily for 4 days before in duction of IBD by 2,4,6-trinitrobenzene sulfonic acid (TNBS)-ethanol enema and were then killed at 2, 6, or 24 hours later. Results: Preexposure to CS significantly potentiated colonic damage induced by TNBS. TNBS-ethanol ene ma caused a pronounced increase in colonic myeloperoxidase activity, leukot riene B-4 level, and also inducible nitric oxide synthase activity, its pro tein, and messenger RNA expression. These parameters were all significantly increased further by exposure to CS. In contrast, increased colonic supero xide dismutase activity after TNBS-ethanol enema was attenuated by CS expos ure. The potentiating effects of CS exposure on TNBS-induced IBD were signi ficantly alleviated after pretreatment with cyclosporin A (an immunosuppres sant), N-G-nitro-L-arginine methylester (a nitric oxide synthase inhibitor) , and dimethyl sulfoxide (a hydroxyl radical scavenger). Conclusions: The r esults show that promotion of neutrophil infiltration and free radical prod uction contributed significantly to the potentiating effect of passive ciga rette smoking on experimental IBD.