In vitro effects of two gold compounds, and D-penicillamine on the production of interferon gamma.
There are contradictory reports on Interferon Gamma (IFN gamma) production by peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA). Since many patients previously studied were on Gold Sodium Thiomalate (GST), Auranofin (Auf), or D-Penicillamine (D-Pen) we have investigated the effects of these drugs on IFN gamma production using PBMC from normal controls (NC), and RA patients off GST, Auf, and D-Pen. Auf in low concentrations enhanced IFN gamma production by PBMC from NC but not RA; GST, and D-Pen had no effect. In other experiments PBMC were stimulated with concanavalin A (CONA A), or phytohemagglutinin (PHA). Auf, and GST inhibited IFN gamma production by CON A - stimulated NC and RA cells; D-Pen had no effect. Auf in low concentrations enhanced IFN gamma production by PHA - stimulated NC cells, but this effect was not seen with RA cells; GST inhibited both RA and NC cell production of IFN gamma, and D-Pen had no effect. Auf has a biphasic effect on IFN gamma production by NC cells with low concentrations being stimulatory or co-stimulatory, possibly by acting on T helper cells. Higher concentrations of Auf and GST, equivalent to those achieved in vivo in the course of therapy, inhibit IFN gamma production. These results suggest that gold therapy may affect IFN gamma production in RA, and could explain discrepancies noted in previous studies.
Harth
M
M
Rheumatic Diseases Unit, University of Western Ontario, London, Ontario, Canada.
Cousin
K
K
McCain
G A
GA
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001310:Auranofin / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology
D010835:Phytohemagglutinins; D003208:Concanavalin A; D006052:Gold Sodium Thiomalate; D001310:Auranofin; D007371:Interferon-gamma; D010396:Penicillamine