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

[Background]: The IL-15/NF-κB 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-κB. 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 οg/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 IFNγ, TNFα, IFNα, 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), IFNγ (p= 0.0207), TNFα (p= 0.0099), IFNα (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 (IFNγ: p= 0.0312; TNFα: p= 0.0312; IFNα: 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. © 2010 SEICAP.Spanish Ministry of Education (FPU, AP2002-2696), Junta de Castilla y León (FPI fellowship), Universidad de Valladolid (FPI fellowship), Instituto de Salud Carlos III, Spanish Ministry of Health (PI 070244 and CES08/016), Fundación IECSCYL, Junta de Castilla y León (SAN-GRS232/B/08), and Phadia Spain.Peer Reviewe