SIGNIFICANTLY INCREASED LEVELS OF NITRIC-OXIDE PRODUCTS IN URINE OF CHILDREN WITH CELIAC-DISEASE

Background: Celiac disease is characterized by morphologic and functio nal aberrations of the small intestinal mucosa, i.e. crypt hyperplasia , villous atrophy, infiltration of intraepithelial lymphocytes, and al teration of permeability. Nitric oxide has been shown to affect mucosa l permeability after ischemia-reperfusion, but little is known about t he regulatory role of nitric oxide in celiac disease. The purpose of t his study was to assess nitric oxide production in children with celia c disease and in control subjects. Methods: The sum of nitrite and nit rate in the urine was measured with a colorimetric method in 137 child ren with a median age of 3 years, 84 patients and 53 reference childre n, all of whom underwent a small intestinal biopsy to confirm or overr ule suspicion of celiac disease. Results: Median urinary nitrite-nitra te concentration in celiac children was 3323 mu M (4147 +/- 1102; mean +/- SEM) at first clinical examination and 2501 mu M (2939 +/- 386) a fter gluten challenge, which was significantly higher than concentrati ons in reference children (1029 mu M; 1174 +/- 116) and in children wi th celiac disease on a gluten-free diet (882 mu M; 1369 +/- 360) (p < 0.0001). Conclusions: A gluten-containing diet is associated with an i ncreased nitrite-nitrate secretion in the urine in children with celia c disease, presumably as a result of nitric oxide synthase activation and nitric oxide production in the diseased small intestinal mucosa.