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P039. Mucosal interleukin-33 levels in patients with moderate to severe ulcerative colitis before and after induction of endoscopic remission by infliximab

M.D. Gundersen1, R. Goll1,2, G. Haraldsen3, J.R. Florholmen1,2, 1University of Tromsø, The Arctic University of Norway, Research group of Gastroenterology and Nutrition, Institute of Clinical Medicine, Tromsø, Norway, 2University Hospital of North Norway, Department of Medical Gastroenterology, Tromsø, Norway, 3Oslo University Hospital, Department of Pathology, Rikshospitalet, Oslo, Norway

Background

Interleukin-33 (IL-33) is a known mediator in inflammatory disease and has been shown to be upregulated in acute lesions of inflammation including ulcerative colitis. Its role is not fully understood, especially its importance in wound and mucosal healing in inflammatory bowel disease [1,2].

Methods

We included 57 patients with moderate to severe ulcerative colitis from the University Hospital of North Norway. Patients were treated with infliximab to clinical and endoscopic remission defined by the ulcerative disease activity index as a score of 2 or less and with an endoscopic sub score of 0 or 1. Mucosal gene expression levels of IL-33 and tumour necrosis factor alpha (TNF-α) levels where determined in colon mucosal biopsies prior to infliximab therapy and at endoscopic remission using real-time PCR. Immunohistochemistry analysis was performed for IL-33 in 10 patients and 10 healthy controls.

Results

No differences in IL-33 mucosal levels were found for the whole study population when comparing active disease with endoscopic remission, however a significant reduction of IL-33 was found in a subgroup of 17 patients (30%) who achieved normalisation of TNF-α expression (fold change 0.44, p value = 0.039). Infliximab therapy was stopped in 55 patients following endoscopic remission, at 1 year follow up 26 patients (47%) where still in disease remission. Immunohistochemistry showed IL-33 positive cells in the acute disease phase localised in the lamina propria, endothelial cells and also in basalcryptcells, the latter was not seen in endoscopic remission or in the healthy controls.

Conclusion

Induction of endoscopic remission by infliximab in patients with ulcerative colitis significantly reduced the mucosal IL-33 levels only when TNF-α was normalised. Our data support the hypothesis of IL-33 as a pivotal mediator of inflammation in ulcerative colitis and is tightly associated to the mucosal expression of TNF-α.

1. Sponheim J, Pollheimer J, Oslen T et al, (2010), Inflammatory bowel disease-associated interleukin-33 is preferentially expressed in ulceration-associated myofibroblasts, Am J Pathol, 2010; 177(6): 2804–2815.

2. Haraldsen G, Balogh J, Pollhemier J et al, (2009), Interleukin-33 - cytokine of dual function or novel alarmin? Trends in Immunology, 2009; 30(5): 227–233.