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

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

Vancouver

Congreso; 16th International Congress of Mucosal Immunology; 2013

BACKGROUND & AIMS.Interleukin (IL)-17A, which is up-regulated in inflammatory bowel disease (IBD) mucosal lesions, and IL-17Fmay form IL-17AA and IL-17FF homodimers or IL-17A/F heterodimers. The role of each IL-17 dimer in IBD is unknown, therefore we studied the effects of IL-17AA, IL-17FF and IL-17-A/F in ulcerative colitis (UC) and Crohn?s disease (CD) mucosa.   METHODS.Inflamed colonic biopsies from 17 IBD patients(6UCand 11CD) were cultured ex vivo withIL-17AA, IL-17FF or IL-17A/F (1ng/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. IL-8 and IL-6 were measured in culture supernatants by ELISA.   RESULTS.IL-17AA, but not IL-17FF, significantly reduced both IL-6 and IL-8 production by inflamed IBD biopsies cultured ex vivo, whereas IL-17A/F decreased IL-8 release by IBD mucosa. No difference was observed between CD and UC. Neither IL-17AA, nor IL-17FF, nor IL-17A/F exerted any effect on IL-6 and IL-8 production by IBD myofibroblasts.   CONCLUSIONS.IL-17AA exerts an anti-inflammatory action on inflamed IBD biopsies cultured ex vivo. Its action is not mediated by myofibroblasts, thereforefurther studies are underway to ascertain which cell type is the main target of IL-17AA in IBD mucosa.