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

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 X 10(7) 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 X 10(-8), 1 X 10(-7), 5 X 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/10(7) cells, 5 minutes, P less than or equal to .025). 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 less than .01; and 15.0% +/- 2.5% v 24% +/- 7%, P less than or equal to .025). VCR, a microtubule inhibitor, showed a significant depression of PMN aggregation at 10(-6), 10(-5), and 10(-4) mol/L (P less than .05), lysozyme release at 10(-4) mol/L (P less than .004), and beta-glucuronidase release at 10(-4) mol/L (P less than .004). In addition, chemotaxis was inhibited by VCR in a dose-dependent manner at all concentrations (10(-7) mol/L, P less than .02; 10(-6) mol/L, P less than .007; 10(-5) mol/L, P less than .006, and 10(-4) mol/L, P less than .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.

Immunological reconstitution and correlation of circulating serum inflammatory mediators/cytokines with the incidence of acute graft-versus-host disease during the first 100 days following unrelated umbilical cord blood transplantation

“…Recovery of neutrophil function was evaluated on days 30 and 90 post UCBT by testing for bacterial killing, 19,20 chemotaxis, 21,22 and superoxide production 21,23 of neutrophils using previously described methods. Bacterial killing capability was measured by a modification of the Quie method.…”

“…21,23 Both patient and control PMNs were compared following PMA stimulation and the incubation with cytochrome C for 10 min at 37°C. Similar tubes containing superoxide dismutase were used as blanks (to determine the non-O 2 − reduction of cytochrome C).…”

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Primes Neonatal Granulocytes for Enhanced Oxidative Metabolism and Chemotaxis

“…Superoxide release was assessed as the SOD sensitive reduction of ferricytochrome C as previously described (15,16). Aliquots of PMN were exposed to various concentrations of GM-CSF for 5-120 rnin at 37°C.…”

Inhibitory Effects of Pentobarbital and Phenobarbital on Human Neutrophil Functions

“…Cyclosporine has been shown to reduce O 2− production by neutrophils [23]. O 2− production of human neutrophils is also inhibited with cyclophosphamide at concentrations 10 and 100 times higher than clinically relevant levels by 4% and 30%, respectively, whereas the drug at clinical concentrations has no effect [24]. Unexpectedly the degree of inhibition of O 2− production obtained by the oxybarbiturates seems greater than that of the immunosuppressants, although we are unable to make a simple comparison.…”