Relationship between arachidonic acid metabolism, myeloperoxidase activity and leukocyte infiltration in a rat model of inflammatory bowel disease

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Abstract
The relationship between14C-arachidonic acid (14C-AA) metabolism, myeloperoxidase activity (MPO) and leukocyte infiltration was studied in a chronic model of inflammatory bowel disease, induced by a single intrectal application of the hapten, trinitrobenzene sulphonic acid (TNB). The colonic damage produced by TNB was accompanied, after 12–36 hours, by a marked increase in MPO, which was directly correlated to leukocyte infiltration, assessed histologically. There was also a marked increase in the metabolism of14C-AA, by homogenates of inflamed colon, to 12-, 15-HETE and 6-keto-PGF1α as indices of lipoxygenase and cyclo-oxygenase metabolism respectively. However, a further increase in MPO-cellular infiltration, between 36–72 hours after TNB, was accompanied by a reduction in 12-and 15-HETE formation. The increase in MPO-cellular infiltration was maintained for up to 3 weeks, at which time both 12-, 15-HETE and 6-keto-PGF1α formation had returned to control levels. These results suggest that these AA metabolites have agreater importance in the acute phase of the inflammatory response induced by TNB compared to the later chronic phase.