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

Abstract

Background: The IL-15/NF- 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- B. Therefore, we studied if ascorbate supplementation to gliadin gliadin-stimulated biopsy culture could down-regulate the mucosal immune response to gliadin in CD. Methods: Duodenal biopsy explants from treated CD patients were gliadin challenged in vitro (100 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 , TNF , IFN , 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 (p = 0.0207), TNF (p = 0.0099), IFN (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 : p = 0.0312; TNF : p = 0.0312; IFN : p = 0.0312; and IL-6: p = 0.0078). Gliadinchallenge 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. © 2010 SEICAP. Published by Elsevier España, S.L. All rights reserve