Do eicosanoids cause colonic dysfunction in experimental E coli O157 : H7 (EHEC) infection?

Background-The pathophysiology of (EHEC) infection remains unclear. Eicosan oids have been implicated as pathophysiological mediators in other colitide s. Aims-To determine if prostaglandin E-2 (PGE(2)) and leukotriene B-4 (LTB4) contribute to mucosal inflammation and dysfunction in EHEC colitis. Methods-Ten day old rabbits were infected with EHEC. For five days after in fection, mucosal synthesis of PGE, and LTB4 was measured in distal colonic tissue from control and infected animals and Cr-51-EDTA permeability was as sessed in vivo. Myeloperoxidase activity was measured and histological infl ammation and damage were assessed at five days in control and infected anim als and after treatment of infected animals with the LTB4 synthesis inhibit or MK-886. In separate experiments, ion transport was measured in Ussing ch ambers, before and after in vitro addition of the cyclooxygenase inhibitor indomethacin. Results-LTB4 synthesis was increased from day 2 after infection onwards and PGE, synthesis was increased on day 3. Mucosal permeability did not increa se until day 5 after infection. MK-886 inhibited colonic LTB4 production bu t did not reduce diarrhoea, inflammation, or mucosal damage. Electrolyte tr ansport was not significantly altered on day 3 after infection. However, bo th Cl secretion and reduced Na absorption found on day 5 were partially rev ersed by indomethacin. Conclusions-Tissue synthesis of PGE, and LTB4 did not correlate temporally with EHEC induced inflammation or changes in mucosal permeability and ion t ransport. Cyclooxygenase inhibition partially reversed ion transport abnorm alities but lipoxygenase inhibition did not affect mucosal inflammation or histological damage. We conclude that the contribution of eicosanoids to mu cosal injury and dysfunction is more complex than previously suggested.