EFFECT OF CYTOTOXIC DRUGS ON MATURE NEUTROPHIL FUNCTION IN THE PRESENCE AND ABSENCE OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

The effects of the cytotoxic drugs, adriamycin, cyclophosphamide, daun omycin (daunorubicin), prednisolone, actinomycin D, azacytidine and vi ncristine at concentrations of 1 muM on mature neutrophil function wer e examined. Up to 5 h incubation with adriamycin, azacytidine, cycloph osphamide, daunomycin and prednisolone had no effect on either luminol chemiluminescence or superoxide secretion. However, after 15 min or 1 h (but not 5 h) incubation vincristine enhanced fMet-Leu-Phe stimulat ed chemiluminescence, whilst after 5 h incubation with actinomycin D t he ability of neutrophils to generate reactive oxidants in response to all stimuli tested was impaired: after 5 h incubation with adriamycin reactive oxidant production was also impaired, but only when fMet-Leu -Phe was used as stimulant. All of the drugs tested except azacytidine inhibited neutrophil oxidant production after 5 h incubation in the p resence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Actinomycin D and cyclophosphamide also inhibited GM-CSF stimulated pr otein biosynthesis. These data indicate that cytotoxic drugs may compr omise the potentially beneficial effects of CSFs on mature neutrophil function during therapy.