Monocyte dependent excited oxygen radical generation in rheumatoid arthritis: inhibition by gold sodium thiomalate

A chemiluminescent assay was used to measure generation of excited oxygen species by peripheral blood monocytes obtained from normal controls (NC) and patients with rheumatoid arthritis (RA). Whole peripheral blood mononuclear cells (PBMC) and adherent cells (AdhC) from RA patients showed a significantly higher chemiluminescent response to opsonized zymosan at certain observation times than cells from NC. There was no significant difference however in response to stimulation by calcium ionophore (CI). Gold sodium thiomalate (GSTM) significantly inhibited the peak response of fresh PBMC and AdhC (from both RA and NC) to zymosan and CI. GSTM inhibited only the peak response of fresh cells to zymosan; by contrast cells cultured with GSTM for 72 h showed inhibition at all time periods. The effect of GSTM was dependent on dosage and duration of incubation with cells. The addition of GSTM after zymosan stimulation did not inhibit chemiluminescence. GSTM appears to act upon cellular events following membrane activation which culminates in the generation of excited oxidative species. These results suggest a mechanism of action for GSTM in RA by inhibition of monocyte and macrophage dependent generation of oxy radicals and related excited oxygen species.