Effects of various anti-inflammatory and anti-rheumatic agents on the synthesis, secretion, and activity of a cartilage proteoglycan-degrading enzyme and other macrophage enzymes

Abstract

Enzymes released from the macrophage have been implicated in the connective tissue loss noted in a number of chronic inflammatory diseases. The effects of 2- and 3-day exposures to glucocorticosteroids, non-steroidal anti-inflammatory drugs and selected anti-rheumatic agents on release of a cartilage proteoglycan-degrading enzyme, and of β-glucuronidase, cathepsin D, and elastase from the thioglycollate-elicited mouse peritoneal macrophage were determined. The synthesis (and/or release) of the cartilage proteoglycan degrading enzyme was markedly inhibited following exposure to dexamethasone, flufenamic acid, chloroquine and gold sodium thiomalate. It was unaffected by exposure to aspirin, naproxen, indomethacin and dl-penicillamine, but was and stimulated by levamisole. Dexamethasone stimulated β-glucuronidase synthesis and release and inhibited elastase synthesis. The synthesis and release of β-glucuronidase, cathepsin D and elastase were not affected by non-toxic concentrations of indomethacin and chloroquine. These results demonstrate that certain anti-rheumatic and anti-inflammatory agents may derive at least a part of their therapeutic effects from the inhibition of enzyme release from the macrophage.