Garzetti G G, Ciavattini A, Muzzioli M, Romanini C
Institute of Obstetrics and Gynecology, G. Salesi Hospital, University of Ancona, Italy.
Cancer. 1999 May 15;85(10):2226-31. doi: 10.1002/(sici)1097-0142(19990515)85:10<2226::aid-cncr18>3.0.co;2-x.
The aim of the current study was to evaluate the in vitro effect of IL-12 on the natural cytotoxicity of peripheral blood mononuclear cells (PBMCs) obtained from patients who underwent adjuvant-based cisplatin polychemotherapy for advanced ovarian carcinoma. The authors also investigated amifostine, a cytoprotective agent that appears to protect against chemotherapy damage to healthy tissues, to determine its effects on natural immune function.
Twenty-one women with advanced ovarian serous cystoadenocarcinoma who underwent adjuvant cisplatin-based polychemotherapy were included in the study, and 20 normal volunteer women matched for age served as controls. Six of the 21 women who underwent polychemotherapy received 1:3 amifostine pretreatment. Blood samples were obtained immediately before the first cycle of cisplatin-based polychemotherapy and within 24 hours after the completion of polychemotherapy infusion to evaluate the natural cytotoxic activity of PBMCs against the K562 cell line and the in vitro responsiveness of cytotoxic cells to interleukin-12 (IL-12).
The in vivo administration of cisplatin-based polychemotherapy significantly reduced the natural killer cytotoxicity of PBMCs toward undetectable levels (2.2+/-3.1 vs. 9.2+/-7.0 lytic units, respectively, after and before cisplatin; P < 0.01), and the in vitro exposure to IL-12 did not increase the cytolytic activity of PBMCs (1.9+/-2.1 lytic units). PBMCs from the 6 patients who received random amifostine pretreatment were shown to have retained natural killer cytotoxicity after in vivo administration of cisplatin polychemotherapy (9.7+/-6.7 vs. 9.6+/-6.0 lytic units, respectively, after and before cisplatin; P = 0.9), and the incubation with IL-12 increased cytotoxic activity (13.4+/-6.9 lytic units) toward the levels observed in PBMCs of controls (14.0+/-4.6 lytic units).
These data suggest that cisplatin-based polychemotherapy reduces the natural cytotoxicity of PBMCs in patients with advanced ovarian carcinoma as well as their in vitro responsiveness to IL-12 incubation. Amifostine demonstrated a protective effect on natural killer cell cytotoxicity and responsiveness to IL-12 in this small cohort of patients.
本研究旨在评估白细胞介素-12（IL-12）对接受基于顺铂的多药联合辅助化疗的晚期卵巢癌患者外周血单个核细胞（PBMC）自然细胞毒性的体外作用。作者还研究了氨磷汀，一种似乎能预防化疗对健康组织造成损伤的细胞保护剂，以确定其对天然免疫功能的影响。
本研究纳入了21例接受基于顺铂的多药联合辅助化疗的晚期卵巢浆液性囊腺癌女性患者，并选取20例年龄匹配的正常志愿者女性作为对照。21例接受多药联合化疗的女性中有6例接受了1:3氨磷汀预处理。在基于顺铂的多药联合化疗的第一个周期前即刻以及化疗输液完成后24小时内采集血样，以评估PBMC对K562细胞系的自然细胞毒性以及细胞毒性细胞对白介素-12（IL-12）的体外反应性。
基于顺铂的多药联合化疗的体内给药显著降低了PBMC的自然杀伤细胞毒性至无法检测的水平（顺铂治疗后和治疗前分别为2.2±3.1和9.2±7.0溶细胞单位；P<0.01），并且体外暴露于IL-12并未增加PBMC的溶细胞活性（1.9±2.1溶细胞单位）。接受随机氨磷汀预处理的6例患者的PBMC在体内接受顺铂多药联合化疗后显示保留了自然杀伤细胞毒性（顺铂治疗后和治疗前分别为9.7±6.7和9.6±6.0溶细胞单位；P = 0.9），并且与IL-12孵育增加了细胞毒性活性（13.4±6.9溶细胞单位），达到对照PBMC中观察到的水平（14.0±4.6溶细胞单位）。
这些数据表明，基于顺铂的多药联合化疗降低了晚期卵巢癌患者PBMC的自然细胞毒性以及它们对IL-12孵育的体外反应性。在这一小群患者中，氨磷汀对自然杀伤细胞毒性和对IL-12的反应性表现出保护作用。
