THE ADDITIVE EFFECT OF CERTAIN DRUGS ON THE CYCLOSPORINE-A INHIBITION OF HUMAN T-CELL PROLIFERATION - STUDIES USING THEOPHYLLAMINE, WARFARIN, VERAPAMIL AND DIPYRIDAMOL

The inhibitory effect of Cyclosporine A (CsA) when combined with theophyllamine, warfarin, verapamil or dipyridamol on in vitro proliferation of human T lymphocyte was investigated. All drugs caused an additional inhibition of PHA activation compared with CsA alone, also when the CD8-negative and -positive subsets were tested separately. This effect was dose-dependent for all drugs. Theophyllamine, verapamil and warfarin had to be added early during PHA-stimulated T-cell activation to cause maximal inhibition. Also when testing the proliferative response in mixed lymphocyte cultures, the drugs showed a dose-dependent additional inhibition compared with CsA alone. CsA alone caused no inhibition of lymphokine-dependent growth of T-cell lines, whereas all four drugs caused a weak inhibition in this test system.