Lymphocyte suppression by rolipram with other immunosuppressive drugs

Pentoxifylline, a nonselective phosphodiesterase inhibitor, has immunomodulatory activity in vitro and in vivo and potentiates the suppressive effects of glucocorticoids and cyclosporine on lymphocyte proliferation in vitro. Since phasphodiesterase isotypes 3 and 4 predominate in lymphocytes, the authors measured the suppressive effect of rolipram alone and in combination with low concentrations of methylprednisolone and calcineurin enzyme inhibitors, compared to that of pentoxlfylline on mitogen-stimulated lymphocyte proliferation. The percent inhibition of³H-thymidine incorporation by both 10^-5 and 10^-6 mol/L concentrations of rolipram were significantly greater than that by both 10^-4 mol/L pentoxifylline and 10^-8 mol/L methylprednisolone. The percent inhibition by the combination of 10^-5, but not 10^-6, mol/L rolipram and methylprednisolone was significantly greater than that by 10^-4 mol/L pentoxifylline and methylprednisolone. Potentiation of the suppressive effects of cyclasporine and tacrolimus by roliprom was less consistent. Measurement of cell culture supernatant concentrations of interferon gamma and interleukin-10 indicate that one of the mechanisms underlying the immunosuppressive activity of rolipram is a significantly disproportionate inhibition of the proinflammatory cytokine, interferon gamma. (C)1999 the American College of Clinical Pharmacology.