Fujita J, Xu G, Miyawaki H, Yamaji Y, Takahara J
First Department of Internal Medicine, Kagawa Medical School, Japan.
Chest. 1995 May;107(5):1350-4. doi: 10.1378/chest.107.5.1350.
We monitored the plasma elastase alpha 1-proteinase inhibitor complex levels in 21 patients with primary lung cancer who received combination chemotherapy with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF), and 15 normal nonsmokers as controls. Of the 21 patients, 14 received combination chemotherapy without rhG-CSF (among them, 6 developed pneumonia) and 7 received combination chemotherapy with rhG-CSF (among them, 1 developed pneumonia). We measured peripheral WBC counts, C-reactive protein (CRP) levels, plasma elastase alpha 1-proteinase inhibitor complex (complex) levels, and complex/WBC values during cancer chemotherapy. In patients who received cancer chemotherapy without rhG-CSF and had no complications (n = 8), WBC values decreased after chemotherapy, and then gradually increased. Complex levels also decreased slightly after chemotherapy and gradually recovered. The value obtained from dividing the complex concentration by WBC count (complex/WBC value) remained stable during cancer chemotherapy. In patients who received cancer chemotherapy with rhG-CSF and had no complications (n = 6), WBC values decreased after chemotherapy, and then rapidly increased to abnormally high values. Complex levels also decreased slightly after chemotherapy and rapidly increased to abnormally high values together with the WBC counts. The complex/WBC values remained stable during cancer chemotherapy. In patients who developed pneumonia during cancer chemotherapy with or without rhG-CSF (n = 7), their complex levels, complex/WBC values, and CRP levels were elevated at the onset of pneumonia. The maximum complex levels (the highest levels during chemotherapy) were significantly higher in patients who received cancer chemotherapy with rhG-CSF and did not develop pneumonia (583.1 +/- 114.5 ng/mL) and in patients who developed pneumonia during cancer chemotherapy (516.7 +/- 113.2 ng/mL), compared with normal nonsmokers (130.2 +/- 5.5, p < 0.01) and patients who received cancer chemotherapy without rhG-CSF and did not develop complications (211.5 +/- 23.3, p < 0.01). The maximum complex/WBC values were not increased in patients who received cancer chemotherapy with rhG-CSF (0.08 +/- 0.01) and patients who received cancer chemotherapy without rhG-CSF (0.092 +/- 0.01, p < 0.01). The maximum complex/WBC values were significantly higher in patients with pneumonia (0.56 +/- 0.12) compared with normal nonsmokers (0.026 +/- 0.002, p < 0.01) and patients without complications. These findings suggest that although rhG-CSF increases total plasma elastase burden, increased release of neutrophil elastase from individual neutrophils does not take place in vivo in the absence of pneumonia.
我们监测了21例接受联合化疗(伴或不伴重组人粒细胞集落刺激因子(rhG-CSF))的原发性肺癌患者以及15名正常不吸烟者(作为对照)的血浆弹性蛋白酶α1-蛋白酶抑制剂复合物水平。21例患者中,14例接受了不使用rhG-CSF的联合化疗(其中6例发生肺炎),7例接受了使用rhG-CSF的联合化疗(其中1例发生肺炎)。我们在癌症化疗期间测量了外周血白细胞计数、C反应蛋白(CRP)水平、血浆弹性蛋白酶α1-蛋白酶抑制剂复合物(复合物)水平以及复合物/白细胞值。在接受不使用rhG-CSF的癌症化疗且无并发症的患者(n = 8)中,化疗后白细胞值下降,然后逐渐升高。复合物水平在化疗后也略有下降并逐渐恢复。化疗期间,复合物浓度除以白细胞计数所得的值(复合物/白细胞值)保持稳定。在接受使用rhG-CSF的癌症化疗且无并发症的患者(n = 6)中,化疗后白细胞值下降,然后迅速升高至异常高值。复合物水平在化疗后也略有下降,并与白细胞计数一起迅速升高至异常高值。化疗期间,复合物/白细胞值保持稳定。在接受或未接受rhG-CSF的癌症化疗期间发生肺炎的患者(n = 7)中,肺炎发作时其复合物水平、复合物/白细胞值和CRP水平均升高。与正常不吸烟者(130.2±5.5,p < 0.01)以及接受不使用rhG-CSF的癌症化疗且未发生并发症的患者(211.5±23.3,p < 0.01)相比,接受使用rhG-CSF的癌症化疗且未发生肺炎的患者(583.1±114.5 ng/mL)以及在癌症化疗期间发生肺炎的患者(516.7±113.2 ng/mL)的最大复合物水平(化疗期间的最高水平)显著更高。接受使用rhG-CSF的癌症化疗的患者(0.08±0.01)和接受不使用rhG-CSF的癌症化疗的患者(0.092±0.01,p < 0.01)的最大复合物/白细胞值未升高。与正常不吸烟者(0.026±0.002,p < 0.01)和无并发症的患者相比,肺炎患者的最大复合物/白细胞值显著更高(0.56±0.12)。这些发现表明,尽管rhG-CSF会增加血浆弹性蛋白酶的总负担,但在没有肺炎的情况下,单个中性粒细胞释放的中性粒细胞弹性蛋白酶在体内不会增加。