Impaired in vitro polymorphonuclear function secondary to the chemotherapeutic effects of vincristine, adriamycin, cyclophosphamide, and actinomycin D.

Publisher Website
Google Scholar
Abstract
The present study investigated the in vitro effect of four different chemotherapeutic agents, namely, cyclophosphamide (CTX), vincristine (VCR), Adriamycin (Adria Laboratories, Columbus, Ohio) (ADR), and actinomycin D (ACT-D) on human polymorphonuclear leukocyte (PMN) function. Human PMNs suspended in phosphate-buffered saline (PBS) at 1 .times. 107 cells/mL were incubated with increasing concentrations of CTX (0, 10-5, 10-4, 10-3 mol/L) or VCR (0, 10-7, 10-6, 10-5, 10-4 mol/L) ADR (0, 10-6, 10-5, 10-4, 10-3, mol/L), or ACT-D (0, 5 .times. 10-8, 1 .times. 10-7, 5 .times. 10-7, and 10-6 mol/L). The cells were then tested for bacterial killing against Staphylococcus aureus, chemotaxis activity stimulated by Escherichia coli endotoxin, N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated aggregation, and cytochalasin B (Cyto B)/FMLP-stimulated superoxide production, and enzyme degranulation. High concentration of CTX, an alkylating agent, showed a significant depression of PMN superoxide production, (124 .+-. 13 v 161 .+-. 15 nmol/107 cells, 5 minutes, P .ltoreq. 0.25). ADR, an intercalating agent and membrane inhibitor, showed a significant depression of PMN degranulation and lysozyme release at 10-4 and 10-3 mol/L (15.3% .+-. 1.7% v 24% .+-. 7%, P < .01; and 15.0% .+-. 2.5% v 24% .+-. 7%, P .ltoreq. .025). VCR, a microtubule inhibitor, showed a significant depression of PMN aggregation at 10-6, 10-5, and 10-4 mol/L (P < .05), lysozyme release at 10-4 mol/L (P < .004), and .beta.-glucuronidase release at 10-4 mol/L (P < .004). In addition, chemotaxis was inhibited by VCR in a dose-dependent manner at all concentrations (10-7 mol/L, P < .02; 10-6 mol/L, P < .007; 10-5 mol/L, P < .006, and 10-4 mol/L, P < .003). ACT-D showed no significant effect on the PMN functions tested. These studies conclude that chemotherapeutic agents have modulating in vitro effects on PMN function. Further in vivo studies are therefore needed to assess PMN abnormalities in patients receiving cancer chemotherapy to determine their role in infectious complications.