Effects of sulphasalazine and its metabolites on neutrophil chemotaxis, superoxide production, degranulation and translocation of cytochrome b‐245

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Abstract
This study describes effects of sulphasalazine, 5-amino-salicylic acid (5-ASA) and sulphapyridine on polymorphonuclear neutrophils. Chemotaxis by polymorphonuclear neutrophils incubated with 5-ASA was reduced in a concentration dependent fashion (10(-5)-10(-4) M). Degranulation and release of lysozyme and beta-glucuronidase by activated polymorphonuclear neutrophils was inhibited by sulphasalazine but inhibited by sulphasalazine (IC50: 2 x 10(-4) M) and to a lesser extent by 5-ASA (IC50: 10(-3) M). Using a cell-free system sulphasalazine was found to be a strong scavenger and 5-ASA and sulphapyridine had only weak effects. Superoxide anion production requires translocation of a cytochrome b-245 and this translocation was reduced by sulphasalazine (P less than 0.01) but not by 5-ASA or sulphapyridine. In conclusion, the intact sulphasalazine molecule has an action of its own and marked differences exist between the action of sulphasalazine and 5-ASA, which may be important for the clinical activity.