Effect of heavy metals on human rheumatoid synovial cell proliferation and collagen synthesis.

The dose-dependent effects of heavy metals on cell proliferation, collagen synthesis, and non-collagen protein synthesis were studied in early passage cultures of human synovial cells exposed to 1-100 microM concentration of gold, silver, mercury, cadmium or lead for 5 days. The incorporation of [3H]thymidine into trichloroacetic acid insoluble material was inhibited 50% by each of the heavy metals at concentrations between 1 and 10 microM. Gold, lead and mercury (10 microM) decreased the DNA content of the cultures by less than 15%; silver (10 microM) and cadmium (10 microM) resulted in decreased DNA content, which was attributed to cytotoxicity. A dose-dependent inhibition of [3H]proline incorporation into bacterial collagenase resistant (non-collagen) protein was observed after incubation with 10 microM mercury, lead and silver. During incubations with 10 microM gold and cadmium, collagenase resistant protein accumulation increased. All the heavy metals except for gold inhibited collagen accumulation to a greater extent than non-collagen protein accumulation. Gold (10 microM) stimulated the amount of collagen produced per cell, and the percentage of collagen to total protein was increased 50%. The rate of collagen accumulation in medium decreased during incubation with 10 microM silver, mercury, cadmium and lead. The stimulation of collagen synthesis may be a unique property of gold related to the therapeutic indices of gold, compared to other heavy metals, in rheumatoid arthritis.