Immunosuppression by Captopril in vitro: Inhibition of Human Natural Killer Activity by Copper-dependent Generation of Hydrogen Peroxide

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The effect of captopril and a mixture of captopril and copper on natural killer (NK) activity of normal human peripheral blood mononuclear cells (PBMC) was examined. Preincubation of PBMC with captopril alone did not affect their NK activity at concentrations of 5-50 μg/ml. However, in the presence of copper sulfate, captopril inhibited the NK activity in a dose-response fashion. Similar inhibition was observed when adherent depleted fraction was treated with captopril and copper. In the time course study, significant inhibition of NK activity by captopril and copper was already observed at 3 hr preincubation. The inhibition of NK activity by captopril and copper was completely abolished by the addition of catalase, but not by superoxide dismutase, interleukin-2, or indomethacin. Preincubation of PBMC with captopril and copper for 18 hr decreased its viability. This decrease was also reversed in the presence of catalase. These results suggest that immunosuppression by captopril in the presence of copper was mediated by hydrogen peroxide.