Cairo M S, Mallett C, VandeVen C, Kempert P, Bennetts G A, Katz J
J Clin Oncol. 1986 May;4(5):798-804. doi: 10.1200/JCO.1986.4.5.798.
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.
本研究调查了四种不同化疗药物，即环磷酰胺（CTX）、长春新碱（VCR）、阿霉素（阿德里亚实验室，俄亥俄州哥伦布市）（ADR）和放线菌素D（ACT-D）对人多形核白细胞（PMN）功能的体外影响。将悬浮于磷酸盐缓冲盐水（PBS）中浓度为1×10⁷个细胞/mL的人PMN与浓度逐渐增加的CTX（0、10⁻⁵、10⁻⁴、10⁻³mol/L）或VCR（0、10⁻⁷、10⁻⁶、10⁻⁵、10⁻⁴mol/L）、ADR（0、10⁻⁶、10⁻⁵、10⁻⁴、10⁻³mol/L）或ACT-D（0、5×10⁻⁸、1×10⁻⁷、5×10⁻⁷和10⁻⁶mol/L）孵育。然后检测细胞对金黄色葡萄球菌的杀菌能力、大肠杆菌内毒素刺激的趋化活性、N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）刺激的聚集以及细胞松弛素B（Cyto B）/FMLP刺激的超氧化物产生和酶脱颗粒。高浓度的CTX，一种烷化剂，显著降低了PMN超氧化物的产生（124±13对161±15 nmol/10⁷个细胞，5分钟，P≤0.025）。ADR，一种嵌入剂和膜抑制剂，在10⁻⁴和10⁻³mol/L时显著降低了PMN脱颗粒和溶菌酶释放（15.3%±1.7%对24%±7%，P＜0.01；以及15.0%±2.5%对24%±7%，P≤0.025）。VCR，一种微管抑制剂，在10⁻⁶、10⁻⁵和10⁻⁴mol/L时显著降低了PMN聚集（P＜0.05），在10⁻⁴mol/L时降低了溶菌酶释放（P＜0.004），在10⁻⁴mol/L时降低了β-葡萄糖醛酸酶释放（P＜0.004）。此外，VCR在所有浓度下均以剂量依赖方式抑制趋化作用（10⁻⁷mol/L，P＜0.02；10⁻⁶mol/L，P＜0.007；10⁻⁵mol/L，P＜0.006，以及10⁻⁴mol/L，P＜0.003）。ACT-D对所检测的PMN功能无显著影响。这些研究得出结论，化疗药物对PMN功能具有体外调节作用。因此，需要进一步进行体内研究，以评估接受癌症化疗患者的PMN异常情况，从而确定它们在感染性并发症中的作用。
