Interleukin (IL)-17A Homodimer Reduces Pro-Inflammatory Cytokine Production By Inflammatory Bowel Disease Mucosa Cultured Ex Vivo

CURCIARELLO RENATA; BIANCHERI PAOLO; GIUFFRIDA PAOLO; MACDONALD THOMAS; DOCENA GUILLERMO H.

Mardel Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

SAi y SAIC

Inflammatory bowel diseases (IBD) are chronic disorders in which pro-inflammatory cytokines are key players in the immunopathogenesis. Interleukin (IL)-17A was found to be up-regulated in mucosal lesions, and IL-17F may form IL-17AA and IL-17FF homodimers or IL-17A/F heterodimers. Since the role of IL-17 dimers is unknown in IBD, we studied the pro-inflammatory effect of IL-17AA, IL-17FF and IL-17-A/F in intestinal samples of ulcerative colitis (UC) and Crohn?s disease (CD) patients. Inflamed colonic biopsies from 17 IBD patients (6 UC and 11 CD) were cultured ex vivo for 24 hours with IL-17AA, IL-17FF or IL-17A/F (1 ng/ml). Mucosal myofibroblasts isolated from the inflamed colon of 4 CD and 4 UC patients were cultured with increasing concentrations (1-100 ng/ml) of each dimer or tumor necrosis factor (TNF)- (20 ng/ml) as control. IL-6 and IL-8 were measured in culture supernatants by ELISA. We found in inflamed IBD biopsies that IL-17AA, but not IL-17FF, significantly reduced both IL-6 and IL-8 production, whereas IL-17A/F only decreased IL-8 release. No differences were observed between CD and UC samples. As expected, TNF- stimulation significantly increased IL-6 and IL-8 production in CD and UC myofibroblasts. However, neither IL-17AA, nor IL-17FF, nor IL-17A/F modified the secretion of IL-6 and IL-8 in IBD myofibroblasts. In conclusion, we found that IL-17AA exerted an anti-inflammatory action on inflamed IBD biopsies, and this effect is not mediated by myofibroblasts. Further studies are needed to identify the cell target for IL-17AA in IBD mucosa.