EFFECTS OF ROLIPRAM AND CI-930 ON IL-2 MESSENGER-RNA TRANSCRIPTION INHUMAN JURKAT CELLS

Interleukin-2 (IL-2) is a major mediator of immunologic responses invo lved in many chronic inflammatory diseases. We have investigated the e ffects of rolipram, a PDE-IV inhibitor, and CI-930, a PDE-III inhibito r, on IL-2 gene expression in the Jurkat human T cell line. The immuno suppressant cyclosporin A (CsA) was included as a positive control. Ju rkat cells were stimulated with 1 mug/ml phytohemagglutinin (PHA) and 50 ng/ml phorbol 12-myristate, 13-acetate (PMA) for 6 h, and mRNA was analyzed using reverse transcription and polymerase chain reaction (RT /PCR). IL-2 transcription was greatly inhibited by 1 muM CsA, whereas neither 10 muM rolipram nor 10 muM CI-930 had any effect on steady-sta te levels of IL-2 mRNA. Therefore, PDE inhibitors do not affect synthe sis of IL-2 mRNA in this model of activated T cells. This is of intere st given that these agents inhibit the proliferation of primary T cell s. For murine splenocytes stimulated by 2.5 mug/ml concanavalin A (Con A), rolipram had an IC50 of 0.09 muM and CI-930 an IC50 of 4.4 muM. T hese concentrations are below those at which IL-2 mRNA synthesis was s hown to be unaffected. Therefore, the mechanism by which inhibitors of PDE-III and PDE-IV affect T cell proliferation is not likely to invol ve suppression of IL-2 mRNA transcription.