Interleukin (IL)-17A Homodimer Reduces Pro-Inflammatory Cytokine Production by Inflammatory Bowel Disease Mucosa Cultured ex vivo

CURCIARELLO R; BIANCHERI P; DOCENA G H; MACDONALD TT

Vancouver, BC

Congreso; 16th International Congress of Mucosal Immunology; 2013

Society of Mucosal Immunology

Background and Aims: Interleukin (IL)-17A, which is up-regulated in inflammatory bowel disease (IBD) mucosal lesions, and IL-17F may 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 (6 UC and 11 CD) were cultured ex vivo with IL-17AA, IL-17FF or IL-17A/F (1ng/ml). Mucosal myofibroblasts isolated from the inflamed colon of 4 CD and 4 UC patients were culturedwith 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-8production by inflamed IBD biopsies cultured ex vivo, whereas IL-17A/F decreased IL-8 release by IBDmucosa. 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. Conclusion: IL-17AA exerts an antiinflammatory action on inflamed IBD biopsies cultured ex vivo. Its action is not mediated by myofibroblasts; therefore further studies are underway to ascertain which cell type is the main target of IL-17AA in IBD mucosa.