P037. Is ulcerative colitis an atypical Th2-mediated disease characterised by excess production of interleukin‑13?
P. Biancheri1, A. Di Sabatino1, F. Ammoscato2, I. Joe-Njoku2, N. Ahmad2, M. Guerci1, P. Giuffrida1, G.R. Corazza1, T.T. MacDonald2
1Fondazione IRCCS Policlinico S. Matteo, University of Pavia, First Department of Medicine, Italy; 2Blizard Institute, Barts And The London School Of Medicine And Dentistry, Centre for Immunology and Infectious Disease, London, United Kingdom
Background: Interleukin (IL)-13 is produced mostly by T helper cell type (Th)2 cells and, together with IL‑5, it has been supposed to be a major cytokine implicated in sustaining the pro-inflammatory immune response in ulcerative colitis. We have therefore assessed IL‑13 and IL‑5 production by inflamed mucosa and isolated lamina propria mononuclear cells (LPMCs) from ulcerative colitis patients, and evaluated the effect of IL‑13 or its neutralization on the intestinal immune response in inflammatory bowel disease.
Methods: Biopsies and LPMCs from the inflamed colon of 11 ulcerative colitis patients and 9 Crohn's disease patients, and from normal colon of 15 control subjects were cultured ex vivo with or without anti-CD3/CD28-antibodies. IL‑13, IL‑5, IL‑17 and interferon (IFN)-gamma production was measured by ELISA in the cell and organ culture supernatants. Anti-CD3/CD28-stimulated LPMCs were also cultured with recombinant human IL‑13 or with an anti-IL‑13 neutralizing antibody, and the production of IFN-gamma, IL‑17 and tumor necrosis factor (TNF)-alpha was determined by ELISA.
Results: Ex vivo IL‑13 production did not differ between ulcerative colitis, Crohn's disease and control biopsies, although IFN-gamma and IL‑17 were significantly higher in ulcerative colitis and Crohn's disease than in controls. Anti-CD3/CD28 stimulation induced a small increase in IL‑13 production without significant differences between the three groups, whereas IFN-gamma and IL‑17 production by LPMCs was significantly higher after anti-CD3/CD28 stimulation. IL‑5 was undetectable in all the organ culture or LPMC supernatants. The addition of recombinant IL‑13 or the neutralization of endogenous IL‑13 did not induce any significant change in IFN-gamma, IL‑17A and TNF-alpha production by anti-CD3/CD28-stimulated ulcerative colitis and Crohn's disease LPMCs.
Conclusions: Our findings do not support a prominent role for IL‑13 and the Th2 response in driving mucosal inflammation in ulcerative colitis.