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Allergol Immunopathol (Madr). 2012 Jan-Feb;40(1):3-8. doi: 10.1016/j.aller.2010.11.003. Epub 2011 Mar 21.

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

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1
Mucosal Immunology Lab, Department of Paediatrics & Immunology, Universidad de Valladolid-CSIC, Spain.

Abstract

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 μg/ml) with and without 20mM ascorbate. An extra tissue explant in basal culture was used as internal control. Secretion levels of nitrites (3h), and IFNγ, TNFα, IFNα, 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), 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.

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PMID:
21420224
DOI:
10.1016/j.aller.2010.11.003
[Indexed for MEDLINE]
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