Background: Recently, has been demonstrated the role of IL-36 cytokines in chronic inflammatory diseases. Phenotypic characterization of IL-36 family members, IL-38 and IL-36Ra producing cells and gene expression is poorly described in patients with inflammatory bowel disease (IBD). Thus, the aim of this study was to characterize tissue expression of IL-38 and their antagonist (IL-36Ra) producing cells regarding to clinical activity in patients with Ulcerative Colitis (UC) and Crohn Disease (CD).
Methods: This is a cross-sectional and comparative study that included 30 active UC, 20 remission UC, 10 active CD, and 10 remission CD and 30 normal controls. Gene expression of IL-38 and IL-36RA were measured by real-time polymerase chain reaction (RT-PCR) after total RNA extraction and complementary DNA was synthesized by PCR. Protein expression was detected by double-staining immunohistochemistry. Statistical analysis was performed using the SPSS 19 program by the Kruskal-Wallis One Way Analysis of Variance on Ranks Data were expressed as the median, range and mean ± SE. A P value ≤0.05 was considered as significant.
Results: The gene expression of IL-38 was increased in colonic tissue from patients with inactive UC when compared with active UC and control group (p=0.009 and p=0.008, respectively). The gene expression of IL-36Ra was significantly higher in colonic tissue of patients with active UC when compared with remission UC and non-inflamed control group (p=0.006 and p=0.007). CD14+/IL-36Ra+ pDCs were determined on higher number on submucosa, muscular, and adventitia from active CD patients compared with active UC patients and non-inflamed control tissue. A small number of epithelial cells from mucosa and perivascular lymphocytes synthesized the IL-36Ra. The IL-38 expression in tissue from patients with UC and CD was mostly by epithelial and connective tissue cells. Nevertheless, some perivascular inflammatory CD123- cells that expressed this cytokine. In addition, there were a small subpopulation of CD123+/IL-38-producing cells distributed along serosa, muscular, submucosa and mucosa. The IL-38-expressing cells were plentiful in serosa, muscular and submucosa from active UC compared to active CD and non-inflamed control tissue. The protein expression of IL-38 was higher in mucosa from IBD patients compared to other layers.
Conclusions: The IL-38 and IL-36Ra were increased in patients with IBD. These cytokines might represent novel therapeutic targets in patients with IBD.