Effect of gold sodium thiomalate on proliferation of human rheumatoid synovial cells and on collagen synthesis in tissue culture

Abstract

Synovial tissue obtained from patients with rheumatoid arthritis who were undergoing reconstructive joint surgery was used to obtain explant cultures of synovial cells. The experiments described were performed on growing monolayer cultures during the second to fifth passages. Synovial cells were exposed to gold sodium thiomalate (GST) in concentrations equivalent to levels attained in synovial tissues during chrysotherapy (3–50 μg/ml). After 5 days of exposure of cells to 10 or 50 μg/ml of GST, [ 3H]thymidine incorporation into DNA was inhibited 94 or 99 per cent, respectively. After 10 days of exposure to 10 μg/ml of GST, cell number was decreased 50 per cent, although no change in cell number was found after a 5-day exposure to 100 μg/ml of GST. The total collagen content of the media was decreased in flasks of cells exposed to 50 μg/ml of GST for 15 days, which reflects the decrease in cell numbers observed at this concentration. However, after 15 days of exposure of synovial cells to 12 μg/ml of GST, incorporation of [ 14C]proline into total collagen per cell increased 4-fold. This increase in [ 14C]proline incorporation occurred predominantly in type I collagen. In these experiments, the percentage of type III collagen containing [ 14C]proline and the amount found in media were suppressed 50 per cent by a fifteen day exposure to 3 μg/ml of GST. The ability of GST to increase the relative commitment of these cultures to make type I collagen is dose dependent in the range from 3 to 12 μg/ml. These data indicate that changes in cell proliferation and in the nature (genetic composition) of the extracellular matrix produced are direct effects of GST on the synovial cell in tissue culture and may represent one important mechanism of action of chrysotherapy in the treatment of patients with rheumatoid arthritis.