Inhibition of neutrophil degranulation and superoxide production by sulfasalazine. Comparison with 5-aminosalicylic acid, sulfapyridine and olsalazine.
Sulfasalazine is a potent inhibitor of superoxide production and granule enzyme release by stimulated neutrophils, and modulation of these responses may contribute to its anti-inflammatory properties. It is a composite drug consisting of 5-aminosalicylic acid and sulfapyridine joined through an azo linkage. To investigate which functional groups on the molecule are active against neutrophil responses, 5-aminosalicylic acid, sulfapyridine and olsalazine were added to cells stimulated with fMet-Leu-Phe or immune complexes. The inhibitory effects of sulfasalazine on superoxide production, degranulation and neutrophil-mediated collagen degradation were closely mimicked by olsalazine, with the other two compounds having little effect on either function. Thus the azo link appears to be the important structural feature of sulfasalazine that affects neutrophil responses. This suggests that sulfasalazine could be anti-inflammatory in its own right rather than just acting as a source of 5-aminosalicylic acid. Our findings are also a favourable indication for olsalazine (Dipentum), which is currently under trial as an anti-inflammatory agent.
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000276:immunology; D005089:Exocytosis / Q000187:drug effects*; D006801:Humans; D019804:Mesalamine; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology*; D013481:Superoxides / Q000096:biosynthesis*
D000636:Aminosalicylic Acids; D000936:Antigen-Antibody Complex; D013481:Superoxides; D012460:Sulfasalazine; D019804:Mesalamine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C032587:olsalazine; D013427:Sulfapyridine