Interleukin-17A Homodimer Reduces Pro-Inflammatory Cytokine Production by Inflammatory Bowel Disease Mucosa Cultured Ex-Vivo.

BIANCHERI PAOLO; DISABATTINO ANTONIO; CURCIARELLO RENATA; AMMOSCATO FRANCESCA; CORAZZA GINO R; JAMES O. LINDSAY; MACDONALD TT

Washington

Congreso; Digestive Disease Week 2015; 2015

Background & Aims: Interleukin (IL)-17A, which is up-regulated in inflammatory bowel disease (IBD) mucosal lesions, andIL-17F are normally present as IL-17AA and IL-17FF homodimers and may occasionally form IL-17A/F heterodimers. Therole of each IL-17 dimer in IBD is currently unknown. Here we studied the effects of IL-17AA, IL-17FF and IL-17-A/F inulcerative 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 for 24 hours withIL-17AA, IL-17FF or IL-17A/F (1 ng/ml). Mucosal myofibroblasts isolated from the inflamed colon of 4 CD and 4 UC patientswere cultured for 24 hours with tumor necrosis factor (TNF)-α 20 ng/ml or with increasing concentrations (1-100 ng/ml) ofIL-17AA, IL-17FF or IL-17A/F. IL-6 and IL-8 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 exvivo, whereas IL-17A/F decreased IL-8 release by IBD mucosa. No difference was observed between CD and UC. NeitherIL-17AA, nor IL-17FF, nor IL-17A/F exerted any effect on IL-6 and IL-8 production by IBD myofibroblasts. As expected,TNF-α stimulation significantly increased IL-6 and IL-8 production by both CD and UC myofibroblasts in vitro. No differencewas observed between CD and UC myofibroblasts.Conclusions: IL-17AA exerts an anti-inflammatory action on inflamed IBD biopsies cultured ex vivo. The action of IL-17AAis not mediated by myofibroblasts, therefore further studies are underway to ascertain which cell type is the main target ofIL-17AA in IBD mucosa.