Low-dose gold compounds inhibit fibroblast proliferation and do not affect interleukin-1 secretion by macrophages.
We examined the effect of low concentrations of gold compounds on the proliferation of human fibroblasts. Gold sodium thiomalate (GST) inhibited both basal and interleukin-1-induced tritiated thymidine incorporation into fibroblasts in a dose- and time-dependent manner. Significant inhibition was observed at the level of 5 micrograms/ml GST, and greater than 50% inhibition was attained at 10 micrograms/ml. These concentrations are attainable in the serum of treated patients. Similar inhibition was observed when less than 1 micrograms/ml auranofin, which is also within a serum-attainable range, was added. Low concentrations of GST (0-10 micrograms/ml) did not affect interleukin-1 secretion from lipopolysaccharide-stimulated human mononuclear phagocytes (M phi) when assessed by both human fibroblast and C3H/HeJ mouse thymocyte proliferation assays. When M phi precultured for 48 hours with GST (0-10 micrograms/ml) were added to the fibroblast culture in the presence or absence of lipopolysaccharide, there was no significant inhibition of M phi-induced DNA synthesis of fibroblasts. In contrast, when fibroblasts were precultured with GST (0-10 micrograms/ml) for 48 hours and freshly separated M phi were added, significant inhibition was observed in M phi-induced fibroblast proliferation at 5 micrograms/ml. These results suggest that low concentrations of GST directly cause a reduction of fibroblast proliferation, but do not affect the capability of M phi for induction of fibroblast proliferation. Therefore, gold compounds may play a role in the inhibition of the growth of rheumatoid pannus by direct inhibition of fibroblast proliferation.
D001310:Auranofin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D007375:Interleukin-1; D006052:Gold Sodium Thiomalate; D001310:Auranofin; D004247:DNA