PGE2 production after angiotensin-converting enzyme inhibition

Using OKT3 monoclonal antibody driven T-lymphocyte proliferation, we investigated the effects of plasma 10, 20 and 30% in cell cultures on the proliferation ex vivo after exposure to captopril or enalapril taken orally by healthy volunteers. We also studied the effects of captopril, angiotensin II and bradykinin in vitro. We observed a plasma dependent dual effect of ACE inhibition both ex vivo and in vitro and of bradykinin in vitro being a stimulated proliferation at low (10% plasma) and a suppression of proliferation at high (30% plasma). The suppression was shown to be PGE2 mediated but the nature of the stimulatory signal is unknown. Proliferation was also suppressed by angiotensin II mediated by PGE2, but angiotensin II had no stimulatory effect. The results indicate that the effects of ACE inhibition on OKT3 mAb driven T-lymphocyte proliferation is plasma dependent, class specific for ACE inhibitors and mediated by both the ACE inhibitor itself and by bradykinin. Furthermore, it was shown that indomethacin in combination with an ACE inhibitor or bradykinin converted a suppressive response into proliferation indicating an immunostimulatory activity by indomethacin.