Significantly increased levels of nitric oxide products in urine of children with celiac disease.

Abstract

Celiac disease is characterized by morphologic and functional aberrations of the small intestinal mucosa, i.e., crypt hyperplasia, villous atrophy, infiltration of intraepithelial lymphocytes, and alteration of permeability. Nitric oxide has been shown to affect mucosal permeability after ischemia-reperfusion, but little is known about the regulatory role of nitric oxide in celiac disease. The purpose of this study was to assess nitric oxide production in children with celiac disease and in control subjects. The sum of nitrite and nitrate in the urine was measured with a colorimetric method in 137 children with a median age of 3 years, 84 patients and 53 reference children, all of whom underwent a small intestinal biopsy to confirm or overrule suspicion of celiac disease. Median urinary nitrite-nitrate concentration in celiac children was 3323 microM (4147 +/- 1102; mean +/- SEM) at first clinical examination and 2501 microM (2939 +/- 386) after gluten challenge, which was significantly higher than concentrations in reference children (1029 microM; 1174 +/- 116) and in children with celiac disease on a gluten-free diet (882 microM; 1369 +/- 360) (p < 0.0001). A gluten-containing diet is associated with an increased nitrite-nitrate secretion in the urine in children with celiac disease, presumably as a result of nitric oxide synthase activation and nitric oxide production in the diseased small intestinal mucosa.