Changes in mononuclear cell function in patients with rheumatoid arthritis following treatment with auranofin.
Gold salts in vitro modulate lymphocyte proliferation to mitogens and antigens and macrophage phagocytosis. These effects are not confined to gold salts; D-penicillamine and chloroquine as well as some of the non-steroidal anti-inflammatory drugs (NSAIDs) have in vivo immunoregulatory effects. Peripheral blood mononuclear cells during treatment with Myocrisin (gold sodium thiomalate, GSTM) show changes that differ from in vitro effects and are related to therapeutic response rather than GSTM administration. This discrepancy between in vitro and ex vivo responses prompted us to measure cellular functions during auranofin therapy. Twenty-nine patients with rheumatoid arthritis took part in a placebo-controlled trial of auranofin. We examined the spontaneous immunoglobulin (IgG and IgM) and IgM rheumatoid factor (IgM RF) production by cultured mononuclear cells, lymphocyte transformation to concanavalin A and macrophage phagocytosis of Candida albicans. There was a significant fall in IgG synthesis (p less than 0.005) and IgM RF synthesis (p less than 0.005) over the first 4 months of treatment, whereas in the control group there were no significant changes. There was no significant change in IgM production. In the auranofin-treated group the lymphocyte response to concanavalin A fell progressively during 6 months of therapy (at 2 months p less than 0.05, at 4 months p less than 0.01, and at 6 months p less than 0.005). Auranofin therapy had variable effects on monocyte phagocytosis of C. albicans. Therefore, in contrast to GSTM, auranofin suppressed both in vitro and ex vivo lymphocyte functions. This effect is probably related to the direct effect of auranofin on lymphocyte membranes.
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002176:Candida albicans / Q000276:immunology; D002986:Clinical Trials as Topic; D003208:Concanavalin A / Q000494:pharmacology; D004311:Double-Blind Method; D006046:Gold / Q000031:analogs & derivatives*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D007136:Immunoglobulins; D003208:Concanavalin A; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold