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.