Effect of auranofin on antibody-dependent cellular cytotoxicity (ADCC) mediated by rat peripheral blood polymorphonuclear leukocytes and mononuclear cells

Abstract

Auranofin and other clinically used gold compounds were evaluated in vitro for effects on antibody-dependent cellular cytotoxicity (ADCC) of L929 fibroblast target cells mediated by adjuvant rat peripheral blood PMNs or mononuclear cells. Auranofin (10 microM) was found to be a potent inhibitor of PMNADCC. In contrast, gold sodium thiomalate (10-100 microM), gold thioglucose (10-1000 microM), and nongold substructures of auranofin (10 microM) were not inhibitory.. In continuous culture, gold sodium thiomalate and relatively low concentrations of auranofin (smaller than or equal to microM) significantly enhanced PMNADCC. Results of pretreatment studies indicate that auranofin's inhibitory activity of PMNADCC is caused by a noncytotoxic effect on PMN function which is not associated with alteration of PMN-target cell contact. In contrast to its inhibitory activity on PMNADCC, auranofin pretreatment of mononuclear cells resulted in enhanced target cell destruction which appeared to correlate with increased mononuclear cell-target cell contact.