Article Text

PDF

PWE-087 Interleukin-17a Homodimer Reduces Pro-inflammatory Cytokine Production By Inflammatory Bowel Disease Mucosa Cultured Ex Vivo
  1. P Biancheri1,2,
  2. A Di Sabatino2,
  3. R Curciarello1,
  4. GR Corazza2,
  5. JO Lindsay3,
  6. TT MacDonald1
  1. 1Centre for Immunology and Infectious Disease, Barts and the London School of Medicine and Dentistry, London, UK
  2. 2First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
  3. 3Centre for Digestive Diseases, Barts and the London School of Medicine and Dentistry, London, UK

Abstract

Introduction Interleukin (IL)-17A, which is up-regulated in inflammatory bowel disease (IBD) mucosal lesions, and IL-17F are normally present as IL-17AA and IL-17FF homodimers and may occasionally form IL-17A/F heterodimers. The role of each IL-17 dimer in IBD is currently 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 for 24 h 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 for 24 h with tumour necrosis factor (TNF)-α 20 ng/ml or with increasing concentrations (1–100 ng/ml) of IL-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 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. As expected, TNF-α stimulation significantly increased IL-6 and IL-8 production by both CD and UC myofibroblasts in vitro . No difference was observed between CD and UC myofibroblasts.

Conclusion IL-17AA exerts an anti-inflammatory action on inflamed IBD biopsies cultured ex vivo . The action of IL-17AA 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.

Disclosure of Interest None Declared.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.