Conkling P R, Chua C C, Nadler P, Greenberg C S, Doty E, Misukonis M A, Haney A F, Bast R C, Weinberg J B
Department of Medicine, Veterans Administration Medical Center, Durham, North Carolina.
Cancer Res. 1988 Oct 1;48(19):5604-9.
The purpose of this investigation was to understand the biological effects of recombinant human tumor necrosis factor used as therapy for cancer. We studied changes in mononuclear phagocyte function following exposure to this cytokine in vitro or in vivo. Tumor necrosis factor increased phorbol myristate acetate-induced hydrogen peroxide production 8- to 20-fold in peripheral blood monocytes and peritoneal macrophages in vitro in a dose-dependent manner. Similarly, tumor necrosis factor increased phorbol myristate acetate-induced peroxide production 2.3-fold in monocytes isolated from nine patients following an i.v. infusion of this cytokine (40 to 200 micrograms/m2). In addition, tumor necrosis factor induced a 2.3-fold increase in tissue factor-like activity in mononuclear phagocytes in vitro. In vivo, tumor necrosis factor induced a trend toward higher procoagulant activity in monocytes, although this change was not statistically significant. We also noted a trend toward increased activated partial thromboplastin times and the presence of fibrin D-dimer in patients treated with tumor necrosis factor, demonstrating activation of the coagulation and fibrinolytic systems. Thus, in vivo treatment of humans with i.v. recombinant human tumor necrosis factor induced functional changes in mononuclear phagocytes similar to those noted with in vitro treatment.
本研究的目的是了解重组人肿瘤坏死因子用于癌症治疗的生物学效应。我们研究了单核吞噬细胞在体外或体内接触这种细胞因子后功能的变化。肿瘤坏死因子在体外以剂量依赖的方式使外周血单核细胞和腹腔巨噬细胞中佛波酯肉豆蔻酸酯诱导的过氧化氢生成增加8至20倍。同样，在静脉输注这种细胞因子（40至200微克/平方米）后，肿瘤坏死因子使从9名患者分离的单核细胞中佛波酯肉豆蔻酸酯诱导的过氧化物生成增加2.3倍。此外，肿瘤坏死因子在体外使单核吞噬细胞中的组织因子样活性增加2.3倍。在体内，肿瘤坏死因子使单核细胞的促凝活性有升高趋势，尽管这一变化无统计学意义。我们还注意到接受肿瘤坏死因子治疗的患者活化部分凝血活酶时间有增加趋势以及存在纤维蛋白D-二聚体，表明凝血和纤溶系统被激活。因此，静脉内给予重组人肿瘤坏死因子对人体进行体内治疗诱导的单核吞噬细胞功能变化与体外治疗时观察到的相似。
