Mesalazine treatment in organotypic culture of celiac patients: Comparative study with gluten free diet

Given the central role of gluten in the pathogenesis of celiac disease (CD), a strict gluten-free diet (GFD) is the only validated treatment able to restore epithelium integrity and eliminate risks of complications. The risk of gluten contamination and the persistence of inflammation, even in patients strictly adhering to GFD, may render this treatment not always effective claiming the necessity of different new solutions. Oxidative and nitrosative stress have been indicated to play a pathophysiological role in CD. Mesalazine (5-ASA), a drug largely used in inflammatory bowel disease, has potent antinflammatory and antioxidant effects. In fact, mesalazine has been shown to decrease in vitro gluten induced cytokine response and it has been used in vivo in some refractory condition. However, its effect has never compared to that of GFD. The present study aimed to address this issue by comparing the ability of mesalazine and GFD in treating gluten-induced inflammation and oxidative stress. These effects were studied on duodenal mucosa biopsy cultures from newly diagnosed CD patients, treated or not in vitro with mesalazine, and CD biopsy cultures from patients on gluten-free diet for at least one year; and a cohort of controls constituted by healty subjects. On these models, the antioxidant cellular defences, the PPARγ, NF-kB and NOS2 proteins levels were studied. This study shows that mesalazine is as effective as GFD in reducing oxidative burst and inducing PPARγ expression; moreover it resulted more effective than GFD in decreasing NF-kB and NOS2 to the levels of controls.