In the recent years, the incidence of inflammatory bowel disease (IBD) has dramatically increased in young subjects, however, the pathogenesis of paediatric IBD is poorly investigated. In this study we aimed to evaluate the cytokine pattern and the phenotype of cytokine producing cells in the intestinal mucosa of paediatric patients affected by Crohn’s disease (CD) or ulcerative colitis (UC) and of non-IBD healthy controls (HC). Cytokine (IL-15, TNF-α, INF-γ) production was analyzed at basal condition and after mitogen stimulation either intracellularly by flow cytometry or in intestinal cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). A higher frequency of enterocytes (EpCam+ cells) was observed in UC patients compared to CD or HC. An expansion of enterocytes producing IL-15 and TNF-α were found in IBD patients compared to HC. A marked expression of IL-15 in the intestinal epithelium of IBD patients was further confirmed by immunohistochemistry. Myeloid dendritic (CD11c+) cells producing TNF-α and INF-γ were increased in IBD biopsies. Unexpectedly, only after a strong mitogen stimulus, as phytohaemagglutinin, the frequency of CD3+ cells producing IFN-γ was increased in IBD compared to control intestinal mucosa. Interestingly, functional studies performed on organ cultures of intestinal biopsies with neutralizing anti-IL-15 monoclonal antibody showed a marked reduction of mononuclear cell activation, proliferation of crypt enterocytes, as well as a reduction of TNF-α release in organ culture supernatants. In conclusion, we found that in the gut mucosa of IBD children both enterocytes and dendritic cells produce proinflammatory cytokines. The over-expression of IL-15 by enterocytes in IBD intestine and the reduced IBD inflammation by IL-15 blockage suggests that this cytokine could be a therapeutic target in IBD.
Background: Nutritional support is very important in the treatment of Paediatric Inflammatory Bowel Disease (IBD). The role of the Mediterranean Diet (MD) has been understudied in children with IBD. The aims of this study were to assess the dietary intakes of IBD children in comparison with healthy controls (HCs), their adherence to MD; and the relationship between inflammation and dietary behaviors. Methods: Paediatric IBD patients in clinical remission and HCs were enrolled. The nutritional status and adherence to the Mediterranean Diet was evaluated through a 3-day food diary and the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED). Results: The analysis of food diaries showed a significantly higher kilocalorie intake in IBD patients compared to HCs (p = 0.012), an increase in carbohydrates (p = 0.015) and in protein intake (p = 0.024). Both IBD and HCs have an intermediate adherence to MD. The comparison between Crohn’s disease (CD) and Ulcerative colitis (UC) patients showed significant difference in protein intake in CD patients (p = 0.047), as well as for vitamin D (p = 0.044) and iron intake (p = 0.023). Interestingly; in IBD patients we found a significant association between adherence to MD and a low level of fecal calprotectin (p = 0.027). Conclusion: Children with IBD in remission have a sub-optimal food intake compared to HCs. MD seems to correlate to decreased intestinal inflammation.
Inflammation inversely correlates to VDBP concentrations and patients with IBD, despite their deficiency in total 25(OH)D, have normal or even higher levels of free 25(OH)D.
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