ANTAGONISTS OF CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE (PDE) ISOZYMES PDE-3 AND PDE-4 SUPPRESS LYMPHOBLASTIC RESPONSE TO HLA CLASS-II ALLOANTIGENS - A POTENTIAL NOVEL-APPROACH TO PREVENTING ALLOGRAFT-REJECTION

As a potential novel approach to preventing renal allograft rejection, we investigated whether the proliferative response of lymphocytes to mismatched HLA class II antigens in mixed lymphocytic culture (MLC) ca n be suppressed by antagonists of cyclic nucleotide phosphodiesterase (PDE) isozymes. Cilostamide, an antagonist of isozyme PDE3 and, to an even greater extent, in combination with rolipram, an antagonist of is ozyme PDE4, markedly suppressed (Delta = -60%; p<0.01) the mitogenic p roliferative response of lymphocytes in MLC to HLA-DR alloantigens fro m unrelated donors. These observations suggest that the selective PDE isozyme antagonists might have potential as novel drugs in ''signal tr ansduction-targeted'' pharmacotherapy of renal transplant rejection.