Enzyme release from human leukocytes and degradation of cartilage matrix effects of antirheumatic drugs

Various antirheumatic drugs were tested in a newly described model of cartilage degradation‐induced by the nonphagocytic release of neutral protease from viable human leukocytes in the presence of aggregated human IgG. Steroidal and nonsteroidal antiinflammatory drugs inhibited the enzyme release process but not neutral protease activity, whereas gold and chloroquine inhibited the enzyme activity without affecting the release process. Several other drugs, known not to have antiinflammatory activity, were inactive. Neutral protease appears to be preformed in neutrophils and not induced by de novo synthesis during phagocytosis. The concentrations at which the antirheumatic drugs were active in vitro correlated with blood levels usually achieved in man. It is suggested that the activity of compounds in the model system described might predict their effect in vivo in rheumatoid arthritis.