Characterization of the direct effects of cyclophosphamide on cell-mediated immunological responses.

The direct immunosuppressive effects of cyclophosphamide were examined by incubating normal guinea-pig mononuclear cells with activated cyclophosphamide prepared from the serum of separate animals which were treated with cyclophosphamide in vivo. Treated cells were subsequently assayed in a panel of tests of cell-mediated immunity either immediately or following recovery during variable periods of incubation. It was found that cyclophosphamide (1) induces changes in lymphocyte functions which are not due simply to cell death; (2) is markedly antiproliferative in mitogen-induced blastogenesis; (3) depresses migration inhibitory factor production only after a delay of several hours and (4) depresses certain cytotoxicity reactions immediately following treatment, such responses are subsequently normalized when the cells are allowed to recover in culture.