Sulfasalazine inhibits lyso-PAF: acetyl-COA acetyltransferase

Sulfasalazine produced a dose-dependent inhibition of the enzymatic synthesis of platelet-activating factor (PAF) in lysates of rat pleural neutrophils, with an IC50 of 50 microM. Major metabolites of sulfasalazine, 5-aminosalicylic acid and sulfapyridine, inhibited this enzymatic synthesis at much higher concentrations. Inhibition of arachidonate 5-lipoxygenase by sulfasalazine and its major metabolites was also observed at higher concentrations (2-3 mM). Because PAF is a potent mediator of inflammatory responses, an inhibition of PAF synthesis by sulfasalazine may contribute to its therapeutic actions in conditions such as ulcerative colitis and rheumatic illnesses.