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

Abstract

SummaryBackground: 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.

Intestinal parameters of oxidative imbalance in celiac adults with extraintestinal manifestations

“…Considering that several nutrients exert antioxidant effects and influence gene expression, they represent a useful approach for nutritional intervention in CD subjects, as confirmed by recent studies in vitro . These studies have revealed phytonutrients and docosahexaenoic acid efficacy in protection against the cytotoxic effect of gliadin[ 53 - 55 ].…”

Celiac & Gluten Intolerance: A Wellness Perspective

“…148 The antioxidant vitamins, polyphenols, carotenoids, lycopene, and quercetin have been shown to inhibit the generation of oxidative species. [149][150][151] Clinical trials should include subjects from the celiac disease population to establish the effects of nutrition supplements on chronic inflammation. Because of the association of CD with other chronic diseases, such as diabetes, and cardiovascular disease, the development of new gluten-free foods should be focused on nutritional balance for the prevention of chronic disease, not merely focused on sensory quality and convenience.…”

Latestin vitroandin vivomodels of celiac disease

“…The addition of ascorbate (vitamin C) to gliadin exposed duodenal biopsies from treated (GFD) celiac patients was associated with diminished production of IFNγ, TNFα, IL-6, IFNα, IL-15 and IL-17. 108 Antibodies targeting the IL-15 receptor or IL-15 itself were successful in inhibiting villous atrophy in one of the IL-15 overexpressing mouse lines 109, 110 .…”