Effect of antineoplastic drugs on human leukocyte-mediated cytotoxicity against herpes simplex virus infected cells.

Abstract

We evaluated the effect of five antineoplastic drugs on the ability of human leukocytes to destroy herpes simplex virus (HSV) infected target cells in the presence of antibody (antibody-dependent cellular cytotoxicity) and in its absence (natural killer cytotoxicity). Leukocytes from healthy volunteers were separated into macrophages, polymorphonuclear leukocytes, and lymphocytes. Adriamycin, cyclophosphamide, prednisone, procarbazine, and vincristine, at various concentrations and incubation periods, were tested for their effects on the natural killer and antibody dependent cellular cytotoxicity of macrophages, lymphocytes, and polymorphonuclear lymphocytes in a 51Cr release microcytotoxicity assay against HSV-infected cells. All drugs at therapeutic concentrations inhibited natural killer and antibody dependent cellular cytotoxicity; an exception was cyclophosphamide, which did not inhibit the natural killer cytoxicity of lymphocytes. The antibody dependent cellular cytotoxicity of macrophages and polymorphonuclear leukocytes appeared to be more than that of lymphocytes. The results of short incubation (2 hours) of the drug with either effector cells or target cells, followed by drug removal, suggests that the drug effect occurred early and predominantly at the effector cell level. Antineoplastic drugs had an inhibitory effect on natural killer and antibody dependent cellular cytotoxicity against HSV-infected cells. This inhibitory action may partially explain the increased susceptibility of patients receiving chemotherapy to developing viral infections.