Hidaka Takao, Akada Shinobu, Teranishi Akiko, Morikawa Hajime, Sato Shinji, Yoshida Yuji, Yajima Akira, Yaegashi Nobuo, Okamura Kunihiro, Saito Shigeru
Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, Sugitani, Toyoma-shi, Toyama 930-0194, Japan.
Cancer Sci. 2003 Sep;94(9):814-20. doi: 10.1111/j.1349-7006.2003.tb01524.x.
The purpose of this study was to clarify the effects of mirimostim (macrophage colony-stimulating factor; M-CSF) on immunological functions after chemotherapy. The percentage of natural killer (NK) cells in peripheral blood mononuclear cells (PBMCs), NK cell activity, T-helper cell 1/T-helper cell 2 (Th1/Th2) ratio, and superoxide anion production by granulocytes (granulocyte function) were measured as immunological parameters before and after chemotherapy in 44 patients with primary ovarian cancer who received at least three consecutive courses of postoperative chemotherapy. Patients were observed during the first course of chemotherapy, and 39 patients who presented grade III or IV neutropenia were entered into this study and randomly allocated to an M-CSF-administered group (group 1; 19 patients) and a non-M-CSF-administered group (group 2; 20 patients) for the second course. For the third course, a crossover trial was conducted. In the observation period, chemotherapy significantly impaired the immunological parameters. In particular, those parameters were significantly decreased at day 14 compared to the level before chemotherapy. The values of the parameters of group 1 were significantly higher than those of group 2. In the course of chemotherapy during which M-CSF was administered, 19 of the 39 patients presented grade IV neutropenia, and received granulocyte colony-stimulating factor (G-CSF) between days 7 and 14. We compared the changes of those immunological parameters in the M-CSF alone group and the M-CSF + G-CSF group, and found that the concomitant use of G-CSF did not further improve the parameters. These results indicate that chemotherapy markedly impaired the immunological functions, and that the administration of M-CSF significantly improved the impaired immunological functions.
本研究的目的是阐明米瑞司亭(巨噬细胞集落刺激因子;M-CSF)对化疗后免疫功能的影响。在44例接受至少三个连续疗程术后化疗的原发性卵巢癌患者中,测量外周血单核细胞(PBMC)中自然杀伤(NK)细胞的百分比、NK细胞活性、辅助性T细胞1/辅助性T细胞2(Th1/Th2)比值以及粒细胞产生超氧阴离子的情况(粒细胞功能)作为化疗前后的免疫参数。在化疗的第一个疗程观察患者,39例出现III级或IV级中性粒细胞减少的患者进入本研究,并随机分为M-CSF给药组(第1组;19例患者)和非M-CSF给药组(第2组;20例患者)进行第二个疗程。对于第三个疗程,进行了交叉试验。在观察期内,化疗显著损害免疫参数。特别是,与化疗前水平相比,这些参数在第14天显著降低。第1组参数的值显著高于第2组。在给予M-CSF的化疗过程中,39例患者中有19例出现IV级中性粒细胞减少,并在第7天至第14天接受了粒细胞集落刺激因子(G-CSF)。我们比较了单独使用M-CSF组和M-CSF + G-CSF组这些免疫参数的变化,发现同时使用G-CSF并未进一步改善这些参数。这些结果表明化疗显著损害免疫功能,而给予M-CSF可显著改善受损的免疫功能。