Influence of chemotherapeutic agents on superoxide anion production by human polymorphonuclear leukocytes.

The effects of 11 chemotherapeutic agents on superoxide anion (O2-) production were examined in human polymorphonuclear leukocytes (PMNL). All drugs, except predonine, were found to suppress O2- production in PMNL. Adriamycin (doxorubicin), mitomycin C, vindesine, cisplatin, etoposide, nimustine, and pepleomycin suppressed O2- production at relatively low drug concentrations, whereas methotrexate, 5-fluorouracil and vincristine suppressed O2- production at high drug concentrations. Time-dependent suppression of O2- production was evaluated in four drugs, namely Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cisplatin, vindesine, and methotrexate. Only Adriamycin showed suppressive effect on PMNL-derived O2- production in a time-dependent manner. Production of O2- by PMNL is a fundamental element for its bactericidal activity. The authors' results showed suppression of O2- production in PMNL in the presence of chemotherapeutic agents. This indicates a relationship between chemotherapy drugs and susceptibility to infection. The influence of chemotherapeutic agents on O2- production by PMNL should thus be taken into consideration when assessing defense mechanisms and susceptibility to infection of patients treated with these drugs.