Resumen de Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in coeliac disease patients
D. Bernardo, B. Martínez-Abad, S. Vallejo-Diez, E. Montalvillo-Delgado, V. Benito, B. Anta, Luis Ignacio Fernández Salazar, Alfredo Blanco Quirós, José Antonio Garrote Adrados, Eduardo Arranz Sanz
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 20mM ascorbate. An extra tissue explant in basal culture was used as internal control. Secretion levels of nitrites (3h), and IFN?, TNF?, IFN?, IL-17, IL-13, and IL-6 (24h) 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). 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.
