Mechanisms of gold resistance

The efficacy of gold treatment in rheumatoid arthritis is hampered by toxicity, most prevalent in early phases, and unresponsiveness which can only be assessed after more than 6 months on therapy. There is some evidence that more severe disease increases the likelihood of drug resistance. No data indicate an altered pharmacokinetics in resistant individuals, although increased dosage of parenteral gold has been claimed effective in uncontrolled studies. Exposure to metals induces cell adaption and resistance in both prokaryotic and eukaryotic cell lines. In particular this has been shown for gold chloride, sodium aurothiomalate and auranofin. Auranofin induces increased synthesis of metallothionein, a low molecular weight cystein-rich peptide with metal-binding and -homeostatic properties. Thus there is experimental evidence suggesting cellular adaptation as a potential mechanism for gold resistance. However, with the possible exception of auranofin, the nature of the processes remains unknown.