Effect of auranofin, a new antiarthritic agent, on immune complex-induced release of lysosomal enzymes from human leukocytes.
Auranofin, an oral chrysotherapeutic agent effective in the treatment of rheumatoid arthritis (RA), was found to be a potent, noncytotoxic inhibitor of IgG-RF immune complex-induced lysosomal enzyme release (LER) from human leukocytes. At a concentration of 1 microg Au/ml (5 microM), auranofin produced a marked reduction in beta-glucuronidase (100%), acid phosphatase (88%), and lysozyme (72%) release. In contrast, gold sodium thiosulfate (GST, an injectable gold compound) had no inhibitory activity on LER at equivalent gold concentrations (i.e., 1 microg Au/ml) and only modest activity (less than 36% inhibition) at concentrations as high as 40 microg Au/ml. The 50% inhibitory dose (LD50) of auranofin on LER was calculated to be 3-4 microM (0.6-0.8 microg Au/ml). Blood gold levels in auranofin-treated RA patients were found to be within the range required for in vitro inhibition of LER, and correlated with decreases in IgG, RF titers, and IgG-RF immune-complex formation in vitro. These results suggest that the therapeutic action of auranofin may be caused, at least in part, by inhibition of LER and/or decreases in immune-complex formation.
D000936:Antigen-Antibody Complex; D006046:Gold / Q000494:pharmacology*; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D012217:Rheumatoid Factor
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D009942:Organometallic Compounds; D006052:Gold Sodium Thiomalate; D006046:Gold; D012217:Rheumatoid Factor