Inhibition of human granulocyte function by methotrexate.
Inhibition of human granulocyte function by methotrexate.
复制标题
甲氨蝶呤抑制人粒细胞功能。
作者：
J. Hyams;M. Donaldson;J. Metcalf;R. Root
接受细胞毒性药物的患者细菌感染的风险增加。药物引起的白细胞减少可能是宿主防御抑制的原因；然而，关于细胞毒性剂对粒细胞抗菌活性的定性影响（如果有的话）的信息很少。由于甲氨蝶呤目前在体内大剂量使用，我们在体外研究了该药物对正常多形核白细胞抗菌和代谢功能的影响。发现正常多形核白细胞的吞噬作用、定量蛋白质碘化和葡萄球菌杀伤作用随着甲氨蝶呤浓度的增加而减少。甲氨蝶呤对这些细胞功能的影响起效迅速，并且通过洗涤细胞很容易逆转，这表明作用部位是在细胞膜上，而不是在核酸合成水平上。将细胞暴露于相似浓度的叶酸或亚叶酸中不会对细菌吞噬作用造成损害，这表明观察到的效应是甲氨蝶呤特有的。产生这些损害的甲氨蝶呤浓度在体内很容易达到，并且可能改变接受这种治疗的患者的抗菌防御能力。
Patients receiving cytotoxic drugs are at an increased risk of bacterial infection. Drug-induced leukopenia may be responsible for depression of host defenses; however, there is little information concerning the qualitative effects, if any, of cytotoxic agents on granulocyte antibacterial activity. Since methotrexate is now being used in massive doses in vivo, we investigated the effects of this drug on antibacterial and metabolic functions of normal polymorphonuclear leukocytes in vitro. Phagocytosis, quantitative protein iodination, and staphylococcal killing of normal polymorphonuclear leukocytes were found to decrease with exposure to increasing concentrations of methotrexate. The effects of methotrexate on these cell functions were rapid in onset and readily reversed by washing the cells, suggesting a locus of action on the cell membrane rather than at the level of nucleic acid synthesis. Exposure of cells to similar concentrations of folic acid or folinic acid produced no impairment of bacterial phagocytosis, suggesting that the observed effects are specific for methotrexate. The concentrations of methotrexate that produced these impairments are readily achieved in vivo and may alter antibacterial defenses in patients receiving this therapy.