Ulcerative colitis is characterized by amplified acute inflammation with delayed resolution

The cause of chronic inflammation in ulcerative colitis (UC) is incompletely understood. Here we tested the hypothesis that an excessive acute inflammatory response to bacteria contributes to the pathogenesis. Acute inflammatory responses were provoked in vivo in UC patients and healthy controls by intradermal inoculation with bacteria. Vascular responses were quantified by laser Doppler. Inflammatory exudates were recovered in superimposed suction blisters and cells measured by polychromatic flow cytometry, cytokines by multiplex array, and inflammatory lipids by mass spectrometry. Vascular responses in UC patients were heightened at 24h after bacterial injection (p=0.03), and remained abnormally high at 48h (p=0.0005) and this amplified response was seen in UC with Gram-positive as well as Gram-negative organisms (p=0.01). The cellular infiltrate over the injection site, composed largely of neutrophils at 4 hours a was greater in UC (p=0.002). At 48h, the increased numbers of cells in UC were composed of neutrophils (p=0.001) and CD4 lymphocytes (p=0.001). The exaggerated inflammation in UC was not a cytokine-driven phenomenon. Exaggerated onset was normalised in patients taking 5- aminosalicylates, accompanied by increased concentrations of hydroxy fatty acids 9-oxo- octadecadienoic acid (OxoODE; p=0.05) and 13-OxoODE (p=0.01) in resolving exudates. In vitro, these compounds suppressed macrophage inflammatory cytokine secretion through PPARgamma; (p