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, daunomycin (daunorubicin), prednisolone, actinomycin D, azacytidine and vincristine at concentrations of 1 microM on mature neutrophil function were examined. Up to 5 h incubation with adriamycin, azacytidine, cyclophosphamide, 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 stimulated chemiluminescence, whilst after 5 h incubation with actinomycin D the 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 presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Actinomycin D and cyclophosphamide also inhibited GM-CSF stimulated protein biosynthesis. These data indicate that cytotoxic drugs may compromise the potentially beneficial effects of CSFs on mature neutrophil function during therapy.