The effects of auranofin on activation and interleukin-2 release from human peripheral blood mononuclear cells.
Auranofin, 30-300 nM causes a concentration-dependent potentiation of phytohaemagglutinin (PHA)-induced interleukin-2 (IL-2) release from human peripheral blood mononuclear cells in culture. At concentrations of auranofin between 1 and 3 microM, PHA-stimulated IL-2 release was inhibited, and the drug is cytotoxic at these concentrations. At concentrations of auranofin which potentiated PHA-induced IL-2 release, it had no effect on [3H]-thymidine incorporation. Auranofin, 3 to 300 nM caused a concentration-dependent increase in the population of peripheral blood mononuclear cells bearing the IL-2 receptor (Tac positive cells). Auranofin, 300 nM caused an increase of approximately 100% in the glutathione level within the resting cells, and also increased the glutathione level in PHA-stimulated cells. We conclude that auranofin acts early in the cell cycle, selectively to increase the release of IL-2 and the expression of Tac. The action of auranofin on cellular glutathione levels may alter the redox state of the cell which is known to be important in the control of transcription factor activation.
Department of Pharmacology, University College London, UK.
I A
IA
Vint
B M
BM
Chain
J C
JC
Foreman
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D001310:Auranofin / Q000494:pharmacology*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D001310:Auranofin; D005978:Glutathione; D013936:Thymidine