Unique properties of auranofin as a potential anti-rheumatic drug.
Gold salts, auranofin (AF), aurothiomalate (ATM) and aurothioglucose (ATG) displayed immunosuppressive action in a series of in vitro assays which mimic the cell-cell interactions thought to occur in rheumatoid arthritis. The gold salts inhibited phytohaemagglutinin (PHA)-induced thymidine incorporation and gamma-IF production by peripheral blood mononuclear cells, as well as IL-2-induced proliferation of PHA-blasts. The separate addition of IL-2 and gamma-IF partly reversed the anti-proliferative effects of ATM and ATG; however, the addition of IL-1 had no effect. ATM and ATG inhibited PHA-stimulated IL-1 production by mononuclear cells but not spontaneous or LPS-induced IL-1 production by adherent monocytes. It was concluded that ATM and ATG inhibited lymphocyte function and lymphocyte-amplification of macrophage function. The anti-proliferative effects of AF were partly reversed by IL-2 but not by gamma-IF or IL-1. AF inhibited PHA-stimulated IL-1 production by mononuclear cells as well as spontaneous and LPS-induced production by adherent cells. It appeared that AF inhibited lymphocyte and macrophage function directly. AF also displayed potential anti-inflammatory activity in that it inhibited PGE2 and collagenase production by proteolytically dispersed rheumatoid synovial cells.
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001310:Auranofin / Q000494:pharmacology*; D006051:Aurothioglucose / Q000494:pharmacology*; D006046:Gold / Q000494:pharmacology*; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins; D006052:Gold Sodium Thiomalate; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold