Celiac.com 03/28/2012 - A clinical research team wanted to determine if adding ascorbate (vitamin C) to gliadin-stimulated biopsy culture could reduce the mucosal immune response to gliadin in people with celiac disease.

Photo: CC - articotropical The research team included D. Bernardo, B. Martínez-Abad, S. Vallejo-Diez, E. Montalvillo, V. Benito, B. Anta, L. Fernández-Salazar, A. Blanco-Quirós, J. A. Garrote, and E. Arranz. They are affiliated with the Mucosal Immunology Lab of the Department of Paediatrics & Immunology at Spain's Universidad de Valladolid-CSIC.

Their quest was fueled by the understanding that the IL-15/NF-κB axis plays a key role in celiac disease. Because ascorbate is known to inhibit effects on NF-κB, the IL-15/NFκB axis looks like a good possible molecular target for reducing gliadin-induced inflammation in celiac disease.

For their study, the team conducted in vitro gliadin challenges (100 μg/ml) on duodenal biopsy explants from treated patients with celiac disease. Challenges were conducted with and without 20mM ascorbate. As an internal control, the team used an extra tissue explant in basal culture.

The team then measured secretion levels of nitrites (3h), and IFNγ, TNFα, IFNα, IL-17, IL-13, and IL-6 (24h) on the supernatants. They measured IL-15 using Western-blot on whole protein duodenal explants.

When the team added ascorbate to in vitro culture gliadin-challenged biopsies, they found that the ascorbate blocked secretion of nitrites (p=0.013), IFNγ (p=0.0207), TNFα (p=0.0099), IFNα (p=0.0375), and IL-6 (p=0.0036), as compared with samples from culture that received no ascorbate.

They also found that the addition of ascorbate reduced cytokine secretion to levels even lower than those observed in basal cultures (IFNγ: p=0.0312; TNFα: p=0.0312; IFNα: p=0.0312; and IL-6: p=0.0078).

Moreover, the gliadin-challenge triggered IL-15 production in biopsies from treated celiac disease patients, while IL-15 was completely blocked in the cultures that received ascorbate.

Interestingly, ascorbate completely blocked IL-15 production even in the only treated celiac disease-patient who showed basal IL-15 production.

From these results, the team concludes that ascorbate reduces the mucosal inflammatory response to gluten in an in vitro biopsy culture. As such, ascorbate might offer supplementary benefits in future celiac disease therapy.

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