Effect of chemotherapeutic agents on metabolic and bactericidal activity of polymorphonuclear leukocytes

Abstract

Blood was obtained on 36 occasions from 12 healthy adult volunteers and the polymorphonuclear leukocytes (PMNL) were separated. PMNL hexose monophosphate shunt activity of whole blood and ability of separated cells to phagocytize and kill E. coli were evaluated when the PMNL were incubated with normal pooled sera and sera containing therapeutic concentrations of either 15 cancer chemotherapeutic drugs singly and in combination or 9 antibiotics. Resting and stimulated HMPS activity was significantly (p less than 0.025 to p less than 0.001) decreased by cyclophosphamide, carmustine (BCNU), high dose prednisone (pred), vinblastine (vinbl) and vincristine (vinc) and significantly (p less than 0.025 to p less than 0.01) increased by combinations of vinc-pred, vinc-predasparaginase, 6-mercaptopurine (6MP)-methotrexate (Mtx) and 6MP-Mtx-pred when compared to controls. No significant differences in HMPS activity of PMNL were found when exposed to various antimicrobial agents singly or in combination. The killing of E. coli by PMNL was significantly (p less than 0.001) decreased when exposed to BCNU, high concentration pred or combinations of 6MP-Mtx-pred, 6MP-Mtx and vinc-vinbl-pred but not when exposed to other chemotherapeutic agents. This study shows a disparity in results obtained when evaluating PMNL function by HMPS activity and bactericidal assay. In addition, a functional impairment in PMNL exposed to various antimetabolites occurred at a time when they exhibited normal morphology.