Effects of gold sodium thiomalate on interferon stimulation of C2 synthesis and HLA-DR expression by human monocytes.
Gamma-interferon (gamma-IFN) is a T cell-derived lymphokine that has potent macrophage-activating properties. It increases Fc receptor density, increases the formation and release of reactive oxygen intermediates, increases the synthesis and release of complement cascade proteins, especially C2 and factor B, and increases class II (HLA-DR) antigen expression. These effects may play a role in the potentiation of inflammation in rheumatoid arthritis. We examined the possibility that gold sodium thiomalate (GST), an effective treatment for rheumatoid arthritis, would inhibit gamma-IFN-mediated stimulation of monocyte/macrophages. GST in concentrations attainable in vivo was shown to inhibit both spontaneous and gamma-IFN-stimulated C2 production up to 50%. GST inhibition could be only partially overcome with increasing concentrations of gamma-IFN. In addition, GST inhibited gamma-IFN-stimulated HLA-DR expression at the highest concentrations tested (20-50 micrograms/ml). GST alone in low concentrations (0.1-5 micrograms/ml) was found to increase HLA-DR antigen expression as quantitated by several methods, including flow cytometry, cell surface enzyme-linked immunosorbent assay, and Western blotting. This GST-stimulated increase in HLA-DR antigen expression paralleled an increased ability of monocytes to present antigen. The mechanism by which low concentrations of GST stimulate HLA-DR antigen expression is unclear, but was shown by 35S-methionine cell labeling not to involve increased HLA-DR protein synthesis.
D002469:Cell Separation; D003175:Complement C2 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006681:HLA-D Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology
D003175:Complement C2; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D006052:Gold Sodium Thiomalate; D007371:Interferon-gamma