THE MODULATORY EFFECT OF DILTIAZEM ON HUMAN IN-VITRO ALLOREACTIVITY WHEN USED ALONE OR IN COMBINATION WITH CYCLOSPORINE-A AND OR METHYLPREDNISOLONE/

The calcium channel blocker diltiazem is often included in post-transp lant regimens in combination with other immunosuppressive drugs such a s cyclosporin A (CyA). It is primarily used because of its antinephrot oxic and antihypertensive effects, so that undesirable side effects in duced by the immunosuppressive therapy can be reduced. Its alleged abi lity to induce direct immunosuppression may explain the encouraging re sults from its clinical use and would appear to encourage a much wider use of this drug. The present study shows the effect of diltiazem on the human in vitro alloresponse when used alone or in combination with cyclosporin A (CyA) and methylprednisolone (MP). The results show tha t, when administered alone, diltiazem exerts a suppressive effect, but only at high, non-therapeutic doses. Interestingly, in combination wi th CyA or MP, diltiazem enhances the suppressive effect of these two d rugs on in vitro alloresponses at lower doses. This additional effect of diltiazem may contribute to better graft survival in clinical trans plantation.