Effect of Isoenzyme Selective Phosphodiesterase Inhibitors on the Proliferation of Murine Thymus and Spleen Cells

The effects of isoenzyme selective phosphodiesterase inhibitors on mitogen-stimulated proliferation of murine thymus and spleen cells was determined. The type 4 phosphodiesterase inhibitors, (rolipram, RO 20-1724 and denbufylline) and the mixed type 3/4 inhibitors, (zardaverine and benzafentrine) produced a concentration-related inhibition of mitogen stimulated thymus and spleen cell proliferation. Combined addition of the type 4 inhibitor, rolipram and the type 3 inhibitor, SK&F 94836 had no antiproliferative effect additional to that of rolipram alone. The thymus cells were more sensitive to the type 4 inhibitors than the spleen cells. The type 3 phosphodiesterase inhibitor, SK&F 94836 significantly inhibited cell proliferation, but only at high concentrations. The type 1 (vinpocetine) and the type 5 (zaprinast) phosphodiesterase inhibitor had no significant effect on proliferation. These results suggest that thymus and to a lesser extent spleen cell proliferation is dependent on the activity of the type 4 phosphodiesterase isoenzyme.