好中球スーパーオキサイド産生能に関する基礎的並びに臨床的研究 第3編 好中球スーパーオキサイド産生能に及ぼす各種抗白血病剤の影響

Previous work, described in part 2 of this study, showed that the superoxide production of neutrophils was suppressed by induction chemotherapy. These findings suggest direct effects of antileukemic agents on intracellular bactericidal activity; however, there is little information available concerning this aspect. The superoxide of neutrophils is one of the active oxygens and it is thought to be one of the major substances related to the intracellular bactericidal activities of neutrophils. This experiment was conducted in order to evaluate the direct effects of antileukemic agents on superoxide production of human neutrophils. The following results were obtained; 1. The effects of antileukemic agents on superoxide production were examined before and after intensification chemotherapy in 14 patients with complete remission. Significant suppression of superoxide production was found 60 minutes after initiation chemotherapy; however, it recovered 24 hours after chemotherapy. 2. In the in vitro system, neutrophils were incubated with antileukemic agents for 3 minutes prior to stimulation by Concanavalin A and Cytochasin D. Among the antileukemic agents examined, Methotrexate, Vincristine and Prednisolone inhibited superoxide production with a concentration dependency. The 50 % inhibition concentrations of these agents were 3.6x10(-4)mol for Methotrexate, 3.2x10(-4)mol for Vincristine and 4.2x10(-4)mol for Prednisolone. Cytosine arabinoside, Neocartinostatine and Cyclophosphamide showed no inhibitory effects on superoxide production. 3. The inhibition of superoxide production by Methotrexate could not be reversed by Folinic acid in the medium. 4. In the cell free superoxide production system consisting of Xanthine plus Xanthine oxidase, Methotrexate and Prednisolone inhibited superoxide production with a concentration dependency. The 50% inhibition concentrations were 1.3x10(-3)mol for Methotrexate and 2.4x10(-3)mol for Prednisolone. 5. In the in vitro system, Methotrexate and Prednisolone were not only inhibitors of superoxide production but also scavengers of superoxide. These results suggest that some antileukemic agents directly inhibit intracellular bactericidal activities, resulting in the susceptibility to infection of patients with acute leukemia.