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 1 beta (IL1 beta) as modulated by interferon gamma (IFN gamma). 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 IL1 beta production by fresh ADC (0-24 h) was significantly higher than that of aged ADC (24-48 h). The addition of IFN gamma 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 IFN gamma, resulting in a marked reduction of TCSA and IL1 beta production. The effects of IFN gamma on the production of IL1 may be important in the pathogenesis of rheumatoid arthritis (RA). The inhibition by GST and Auf of IFN gamma modulation may contribute to the therapeutic efficacy of these drugs in RA.
Harth
M
M
Rheumatic Diseases Unit, University of Western Ontario, London, Canada.
McCain
G A
GA
Cousin
K
K
D001310:Auranofin / Q000494:pharmacology; D002470:Cell Survival; D006046:Gold / Q000494:pharmacology*; D006052:Gold Sodium Thiomalate / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D006052:Gold Sodium Thiomalate; D001310:Auranofin; D006046:Gold; D007371:Interferon-gamma