The production of an amine-modified derivative of 5-aminosalicylic acid by activated neutrophils. Roles for myeloperoxidase and chloride ions.

Following incubation with activated neutrophils, two metabolites of 5-aminosalicyclic acid (5-ASA) were identified by HPLC. These two metabolites accounted for approximately 60% and 20% of the original 5-ASA. The formation of the major metabolite was prevented by pre-incubation with the peroxidase inhibitor, azide, and reduced by the omission of chloride ions from the incubation medium, or the presence of catalase. A similar product was generated by sodium hypochlorite or myeloperoxidase/H2O2, mass spectroscopical analysis being consistent with it being 5-nitroso-salicylate. Our finding suggests that the efficacy of 5-ASA results from its ability to react with and so scavenge hypochlorite ions. The amount of amine-modified 5-ASA in the faecal stream may thus provide an indicator for hypochlorite production in the bowel.