Studies of the effect of D-penicillamine and sodium aurothiomalate therapy on superoxide anion production by monocytes from patients with rheumatoid arthritis: evidence for in vivo stimulation of monocytes.

The capacity of monocytes from patients with rheumatoid arthritis to generate superoxide anion in vitro after stimulation with serum treated zymosan (STZ) or IgG treated zymosan (IgTZ) was studied before and during therapy with penicillamine (n = 9) or sodium aurothiomalate (AuTM) (n = 12). Significant increases in rates of STZ (p less than 0.01) and IgTZ (p less than 0.02) stimulated superoxide anion production were seen after successful therapy (14 patients), which were paralleled by a significant increase in serum thiol levels. Patients who did not respond clinically to therapy (n = 4) showed a smaller mean increase in serum thiol levels and had high mean rates of in vitro superoxide production before and after second-line therapy. Three patients were withdrawn from the study. The data suggest that successful therapy with penicillamine or AuTM may be associated with monocyte activation, and possible mechanisms are discussed.