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P069 Interleukin 35 and 37 Intestinal Expression and Peripheral Synthesis by Subsets of Regulatory Cells in Patients with Inflammatory Bowel Disease.

G. Fonseca Camarillo*1, F.-C. Janette2, Y.F. Jesús Kazuo3

1Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán. México D.F, México., Inflammatory Bowel Disease Clinic. Department of Gastroenterology. , Distrito Federal, Mexico, 2Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán. México D.F, México., Department of Gastroenterology, Mexico City, Mexico, 3Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán. México D.F, México., Inflammatory Bowel Disease Clinic. Department of Gastroenterology., Mexico City, Mexico

Background

Inflammatory Bowel Disease is characterized by an imbalance between the effectors and regulatory mediators of intestinal immunity with preponderance of pro-inflammatory cytokines. Decrease production of regulatory cytokines such as: IL-10, IL-35 and IL-37 Results in inflammation and autoimmune disease. However, IL-35 and IL-37 intestinal expression and peripheral synthesis by regulatory cells in IBD patients has not been yet described.

Methods

We studied a total of 149 patients divided in different groups: 38 active UC, 31 inactive UC, 17 active CD, and 13 inactive CD and 50 individuals as control group. Gene expression was measured by real time polymerase chain reaction (RT-PCR). Protein expression was detected in tissue by immunohistochemistry and in freshly isolated peripheral blood mononuclear cells by flow cytometry. Descriptive statistics were performed, and categorical variables were compared using the χ2 test or Fisher's exact test. One way analysis of variance on ranks by Holm-Sidak Method and Dunn's test was performed for all pairwise multiple comparison procedures. Statistical analysis was done using the Sigma Stat 11.2 program. Data were expressed as the median, range, and mean ± standard deviation (SD)/standard Error of the mean (SEM). A p value < 0.05 was considered as significant.

Results

The IDO, IL-35 (p35-EBI3 subunits) and IL-37 gene expression was significantly increased in patients with active IBD versus inactive disease and control group (P<0.05). The IL-37 high expression was significantly associated with a mild clinical course of UC characterized by long-term remission (P= 0.03, OR=0.09, IC 95%: 0.01-0.47). Conversely, UC patients in remission had significantly higher IL-10 gene expression compared with active UC patients (P<0.001) control group and CD patients (P<0.001).However, IDO, IL-35 and IL-37 -producing cells were only increased in active CD versus active UC and non-inflamed tissues (P<0.05). The IL-35 was produced by intestinal B regulatory cells and circulating T regulatory cells in patients with inactive disease (P< 0.05). The IL-37 was synthesized by peripheral activate and regulatory B cells, natural killers and monocytes

Conclusion

This is the first depiction of the expression and peripheral production by regulatory cells IL-35+ and IL-37+ in IBD. These Results suggest that tolerogenic mechanisms in IBD patients might be based on the increase of IL-35 and IL-37-expressing by T and B regulatory cells. Additional studies about IL-35 and IL-37 in the gut mucosal immune response and epithelial restitution can begin to support the immunoregulatory role of these cytokines in patients with IBD.