P043 Ulcerative colitis is characterised by an exaggerated onset of acute inflammation with delayed resolution

Background: The early inflammatory response in ulcerative colitis (UC) has been shown to be protracted. We used an in vivo bacterial challenge model to determine the cellular and molecular determinants and consequences of this perturbed acute inflammatory response in patients with UC.
Methods: Acute inflammation was provoked in 26 UC patients off treatment or on 5-aminosalicylates, and 17 healthy controls (HC), by intradermal injection with UV-killed E. coli or S. pneumoniae. The local vascular reaction was quantified using laser Doppler imaging. The early and resolving inflammatory exudates were sampled by raising suction blisters over inoculation sites after 4h or 48h. Cells were characterised by polychromatic flow cytometry; cytokines by multiplex array; and lipid mediators by mass spectrometry. In vivo findings were confirmed by in vitro stimulation experiments on cultured peripheral blood-derived neutrophils and macrophages.
Results: UC patients off treatment demonstrated enhanced local blood flow within 24h of bacterial exposure, with impaired resolution, to both Gram-negative and Gram-positive bacteria (p=0.01).