THE MODULATION OF INTERLEUKIN-1 PRODUCTION BY INTERFERON-GAMMA, AND THE INHIBITORY EFFECTS OF GOLD COMPOUNDS

We have studied the in vitro effects of gold sodium thiomalate (GST) and auranofin (Auf) on the production of interleukin 1 (IL1) expressed as thymocyte co-stimulatory activity (TCSA), and interleukin 1β(IL1β) as modulated by interferon γ(IFNγ). Adherent cells (ADC), of which 80% were monocytes, were obtained from human peripheral blood, and stimulated with lipoprotein polysaccharide (LPS) for 24-48 h. TCSA and IL1β production by fresh ADC (0-24 h) was significantly higher than that of aged ADC (24-48 h). The addition of IFNγ to ADC cultures, however, maintained the capacity of aging ADC to respond optimally to LPS. The addition of GST or Auf inhibited this modulatory effect of IFNγ, resulting in a marked reduction of TCSA and IL1β production. The effects of IFNγ on the production of IL1 may be important in the pathogenesis of rheumatoid arthritis (RA). The inhibition by GST and Auf of IFNγ modulation may contribute to the therapeutic efficacy of these drugs in RA. © 1990.