The effects of the antiglucocorticoid RU486 on the expression of low and high affinity interleukin-2 receptors (IL-2R) in phytohaemagglutinin (PHA)-activated human peripheral blood lymphocytes were investigated. We demonstrated that RU486 inhibits in a dose-dependent way the expression of both classes of IL-2R, thereby mimicking the effects of the glucocorticoid agonist dexamethasone. The maximal effect on the low affinity binding sites was observed at 10 microM (28 +/- 2% of control, P less than 0.001) and on the high affinity IL-2R at 1 microM (from 2938 +/- 74 to 437 +/- 108 binding sites per cell, P less than 0.001). This inhibition of IL-2R expression occurs at a pretranslational level since RU486 decreased the accumulation of beta-chain IL-2R mRNA transcripts. Our data support the concept that the antiglucocorticoid RU486 at pharmacological concentrations can exert agonistic-immunosuppressive effects.
PIP: The effects of RU-486, which has anti-glucocorticoid properties, on expression of the interleukin-2 receptors (IL-2R) in human lymphocytes were examined in terms of its dose effect on 2 types of binding sites, and its suppression of beta-chain IL-2R messenger RNA production. Human peripheral lymphocytes stimulated with phytohemagglutinin (PHA) were incubated with the synthetic glucocorticoid dexamethasone and with RU-486 at various doses. Synthesis of 2 types of IL-2R was measured by immunofluorescence assay of the alpha chain. RU-486 inhibits in a dose- dependent fashion the expression of both classes of IL-2R, acting like an agonist. Maximal suppression was seen at a concentration of 10 mcM for the low affinity binding site, and at 1 mcM for the high affinity rate. Messenger RNA was determined by extracting RNA, fractioning it by electrophoresis on agarose gel, and hybridizing with cDNA probes inserted with a plasmid. RU-486 significantly lowered the accumulation of beta-chain IL-2R mRNA transcripts. Thus RU-486 at pharmacological concentrations acts like a glucocorticoid agonist with immunosuppressive effects.