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. 2000 Jun;46(6):806–812. doi: 10.1136/gut.46.6.806

Do eicosanoids cause colonic dysfunction in experimental E coli 0157:H7 (EHEC) infection?

C Bell 1, E Elliott 1, J Wallace 1, D Redmond 1, J Payne 1, Z Li 1, E O'Loughlin 1
PMCID: PMC1756446  PMID: 10807892

Abstract

BACKGROUND—The pathophysiology of enterohaemorrhagic Escherichia coli (EHEC) infection remains unclear. Eicosanoids have been implicated as pathophysiological mediators in other colitides.
AIMS—To determine if prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) contribute to mucosal inflammation and dysfunction in EHEC colitis.
METHODS—Ten day old rabbits were infected with EHEC. For five days after infection, mucosal synthesis of PGE2 and LTB4 was measured in distal colonic tissue from control and infected animals and 51Cr-EDTA permeability was assessed in vivo. Myeloperoxidase activity was measured and histological inflammation and damage were assessed at five days in control and infected animals and after treatment of infected animals with the LTB4 synthesis inhibitor MK-886. In separate experiments, ion transport was measured in Ussing chambers, before and after in vitro addition of the cyclooxygenase inhibitor indomethacin.
RESULTS—LTB4 synthesis was increased from day 2 after infection onwards and PGE2 synthesis was increased on day 3. Mucosal permeability did not increase until day 5 after infection. MK-886 inhibited colonic LTB4 production but did not reduce diarrhoea, inflammation, or mucosal damage. Electrolyte transport was not significantly altered on day 3 after infection. However, both Cl secretion and reduced Na absorption found on day 5 were partially reversed by indomethacin.
CONCLUSIONS—Tissue synthesis of PGE2 and LTB4 did not correlate temporally with EHEC induced inflammation or changes in mucosal permeability and ion transport. Cyclooxygenase inhibition partially reversed ion transport abnormalities but lipoxygenase inhibition did not affect mucosal inflammation or histological damage. We conclude that the contribution of eicosanoids to mucosal injury and dysfunction is more complex than previously suggested.


Keywords: enterohaemorrhagic; Escherichia coli; electrolyte transport; prostaglandins; leukotrienes; chloride secretion

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Figure 1  .

Figure 1  

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(A) Distal colonic mucosal PGE2 synthetic capacity in uninfected control rabbits and in EHEC infected rabbits 1-5 days after inoculation. Data are mean (SEM), n=12 per group. *p<0.05 compared with control, day 1 infected, and day 2 infected values. (B) Distal colonic mucosal LTB4 synthetic capacity in uninfected control rabbits and in EHEC infected rabbits 1-5 days after inoculation. Data are mean (SEM), n=12 per group. *p<0.05 compared with control and day 1 infected values. (C) Distal colonic mucosal 51Cr-EDTA permeability in uninfected control rabbits and in EHEC infected rabbits 2-5 days after inoculation. Data are mean (SEM), n=4 per group. *p<0. 05 compared with control and other infected values. Lower panels show Cl transport and infiltration of the mucosa by neutrophils. Abs'n, absorption.

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