NITRIC-OXIDE AND INFLAMMATORY BOWEL-DISEASE - EVIDENCE FOR LOCAL INTESTINAL PRODUCTION IN CHILDREN WITH ACTIVE COLONIC DISEASE

Background: Active colitis in patients with inflammatory bowel disease is associated with mucosal vasodilation, increased intestinal permeab ility and abnormal colonic motility. Nitric oxide is a messenger molec ule with many functions, including regulation of local blood flow, vas omotor tone, and inflammation. Increased nitric oxide production and i nducible nitric oxide synthase activity have been demonstrated in expe rimental models of colitis. This study was designed to determine the r elationship between nitric oxide production and colonic inflammation i n children with active colitis and in control subjects and whether exp ression of inducible nitric oxide synthase protein is demonstrable in the intestinal epithelium of these patients. Methods: Nitrate + nitrit e were measured in urine, stool, and plasma using the Griess assay. Ex pression of inducible nitric oxide synthase protein in intestinal tiss ue was determined by immunohistochemical localization. Results: Urinar y nitrate + nitrite levels were not significantly different in patient s and control subjects, In contrast, stool and plasma nitrate + nitrit e concentrations were significantly higher in children with inflammato ry bowel disease compared with levels in control children (stool: 162. 4 +/- 31.0 mu mol/l versus 77.2 +/- 22.1 mu mol/l; plasma: 65.2 +/- 9. 9 mu mol/l versus 38.1 +/- 6.6 mu mol/l; p < 0.05). Stool nitrate + ni trite levels significantly correlated with plasma values. Immunohistoc hemical staining of colonic tissue from children with inflammatory bow el disease demonstrated inducible nitric oxide synthase protein locate d exclusively in epithelial cells. Conclusion: Increased nitric oxide production and enhanced intestinal epithelial cell expression of induc ible nitric oxide synthase protein are associated with active colonic inflammation. (C) 1998 Lippincott-Raven Publishers.