Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in coeliac disease patients

Background: The IL-15/NF-kappa B axis has an important role in coeliac disease (CD) and may represent a molecular target for immunomodulation. Ascorbate (vitamin C) is known to show inhibitory effects on NF-kappa B. Therefore, we studied if ascorbate supplementation to gliadin gliadin-stimulated biopsy culture could down-regulate the mucosa( immune response to gliadin in CD. Methods: Duodenal biopsy explants from treated CD patients were gliadin challenged in vitro (100 mu g/ml) with and without 20 mM ascorbate. An extra tissue explant in basal culture was used as internal control. Secretion levels of nitrites (3 h), and IFN gamma, TNF alpha, IFN alpha, IL-17, IL-13, and IL-6 (24 h) were measured on the supernatants. IL-15 was assayed by western-blot on whole protein duodenal explants. Results: The addition of ascorbate to in vitro culture gliadin-challenged biopsies blocked the secretion of nitrites (p = 0.013), IFN gamma (p = 0.0207), TNF alpha (p = 0.0099), IFN alpha (p = 0.0375), and IL-6 (p = 0.0036) compared to samples from non-ascorbate supplemented culture. Cytokine secretion was downregulated by ascorbate even to lower values than those observed in basal cultures (IFN gamma: p = 0.0312; TNF alpha: p = 0.0312; IFN alpha: p = 0.0312; and IL-6: p = 0.0078). Gliadin-challenge induced IL-15 production in biopsies from treated CD patients, while the addition of ascorbate to culture medium completely inhibited IL-15 production. Moreover, the inhibition of IL-15 by ascorbate took place even in the only treated CD-patient who had basal IL-15 production. Conclusions: Ascorbate decreases the mucosal inflammatory response to gluten in an intestinal biopsy culture model, so it might have a role in future supplementary therapy in CD. (C) 2010 SEICAP. Published by Elsevier Espana, S.L. All rights reserved.