| Intestinal motility, epithelial permeability, electrolyte and fluid secretion, mucus release, and rapid epithelial turnover provide mechanisms of intestinal defence. Alterations in this defence system may increase susceptibility to infection or inflammation. Inflammatory bowel disease is often characterized by periods of remission and relapse. In addition, many post-infectious irritable bowel syndrome patients report symptoms of abdominal pain and diarrhea well after infection. Given that epithelial function (i.e., permeability, electrolyte secretion and mucus release) plays a critical role in mucosal defence, we investigated whether a bout of colitis could cause long-term changes in epithelial function that increase the susceptibility to infection/inflammation.; Six weeks after the induction of colitis in the rat, the colon appeared macroscopically and histologically normal, and no changes in epithelial permeability or mucus secretion were detectable. Despite the absence of damage, the colonic epithelium was hypo-responsive to several secretagogues with respect to electrolyte and fluid secretion in vitro and in vivo. Small intestinal, but not extra-intestinal, inflammation also caused similar epithelial dysfunction. This epithelial dysfunction was at least partially mediated by nitric oxide (NO) derived from the inducible nitric oxide synthase (iNOS) enzyme. Altered epithelial function was also associated with increased colonic bacterial colonization, bacterial translocation and increased epithelial cell proliferation.; These results demonstrate that intestinal inflammation results in prolonged impairment of colonic epithelial secretion. This may contribute to increases in bacterial load and bacterial translocation. Epithelial dysfunction could underlie an increased propensity for further inflammation or infection.; In another study, the role of NO, a free radical proposed to contribute to tissue injury, was examined. The results of this study demonstrated that NOS inhibitors do not ameliorate damage in an experimental model of colitis. This may be due to other free radicals such as hydroxyl radical being produced in greater amounts concomitantly with a reduction in NO production. Thus, NO may be beneficial in preventing tissue injury as a free radical scavenger, rather than harmful as a source of toxic nitrogen-derived species. Examining the oxidative state of the tissue may be essential in predicting whether inhibitors of NOS are beneficial or harmful in inflammation. |
