Effect of anti-rheumatic drugs on the release of lysosomal enzymes from human leukocytes

Abstract

The release of lysosomal enzymes from human polymorphonuclear neutrophils (PMN) into the extracellular medium was selectively induced by the phagocytosis of zymosan particles. The "in vitro" effect on the release of lysosomal enzymes was determined for eight different substances used in the therapy of rheumatoid arthritis. Prednisolone and the three non-steroidal anti-rheumatic agents indomethacin, diclofenac and benoxaprofen only inhibited the release of various lysosomal enzymes at the elevated concentrations of 20-200 micrograms/ml. Of the four drugs examined which are used in basis therapy, Chloroquine and Levamisole exhibited the most clear-cut inhibition of the enzymes (at 20-200 micrograms/ml). The effect of gold salts was uncertain and D-penicillamine only inhibited the release of myeloperoxidase. The release of lysosomal enzymes from neutrophils is then largely resistant to anti-rheumatic agents--at least in the range of therapeutic concentrations. On the basis of these experimental results it seems questionable whether the relatively weak inhibition of lysosomal enzymes observed "in vitro" can contribute to the anti-rheumatic efficacy in patients of the drugs examined.