Time course of nitric oxide synthase generation after gluten exposure in the rectal mucosa of gluten-sensitive patients.

BACKGROUND: Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in order to determine the role of inducible and constitutive nitric oxide synthases in the pathogenesis of this process. MATERIAL: Nine patients with confirmed celiac disease and five healthy controls underwent a long-term rectal gluten challenge (48 h) after an enema of 6 g of crude gluten, and constitutive and inducible nitric oxide synthase activity were determined in rectal biopsies. The histological localization of inducible nitric oxide synthase was determined by immunohistochemistry. RESULTS: Activity of both isoforms of nitric oxide synthase in control subjects did not change significantly after gluten instillation. In celiac patients, constitutive nitric oxide synthase on rectal mucosa also showed no significant changes after challenge with gluten. Inducible nitric oxide synthase isoform exhibited a modest increase 4 h after gluten instillation in celiac patients (mean increase 35% compared with baseline levels) but, 8 h after challenge, generation of iNO synthase was significantly higher: 54% more than pre-challenge production (P < 0.05) and higher than control values (P < 0.05). Inducible nitric oxide synthase staining was mostly localized in mononuclear cells of the epithelium and the lamina propria. After gluten instillation, the enhanced staining was mainly localized in subepithelial areas of the lamina propria. CONCLUSION: Our data suggest a role for nitric oxide, generated by inducible nitric oxide synthase, in the process of rectal mucosa injury by local gluten instillation in sensitized patients. We could not, however, determine if the role of nitric oxide in the ensuing injury of this gluten-induced immune inflammation model is a protective one, or merely a by-product generated by the activation of the inflammatory cells.

Effect of treatment on bone mass, mineral metabolism, and body composition in untreated celiac disease patients.

BACKGROUND/AIMS: Osteopenia is a common complication of celiac disease. The aims of this study were to evaluate whether treatment produces bone remineralization and whether calcium and vitamin D supplementation are necessary to reduce osteopenia. METHODS: Bone mineral density and biochemical parameters of bone and mineral metabolism were measured in 14 newly diagnosed adult celiac disease patients. All patients were treated with a gluten-free diet and were randomized to receive diet only (n = 7) or diet plus calcium (1.0 g/day) and vitamin D (32,000 IU/wk) supplementation (n = 7). Bone density was measured at baseline and at 6 and 12 months of follow-up. Tests for biochemical determinations were repeated every 3 months. RESULTS: At diagnosis, 11 patients had evidence of osteopenia (> 1 SD below normality) in the spine and total skeleton. After 12 months of gluten restriction, overall bone mass had increased 5.0% (p < 0.01) in the lumbar spine and 5.0% (p < 0.002) in the total skeleton. When one only considers those 11 patients who strictly followed gluten restriction, bone density increased 8.4% in the lumbar spine and 7.7% in the total skeleton. Remineralization occurred throughout the skeleton but was more pronounced in the axial than in the peripheral skeleton. The increase in bone mass was independent of age or menopause. Remineralization in patients treated with diet only was similar to that of patients treated with diet and supplements. Basal biochemical parameters showed a high bone turnover with secondary hyperparathyroidism. Treatment induced a decrease in bone turnover activity. However, a complete restoration of biochemical parameters was not achieved. CONCLUSIONS: Strict gluten avoidance promoted a significant increase in bone mineral density. However, values still remain markedly low after 1 yr in several patients. Although calcium and vitamin D supplementation did not provide additional benefit to that obtained by diet alone in the doses administered, our results do not preclude a possible effect of vitamin D at higher dose.