Droemann D, Hansen F, Aries S P, Braun J, Zabel P, Dalhoff K, Schaaf B
Medical Clinic, Research Center Borstel, Borstel, Germany.
Respiration. 2006;73(3):340-6. doi: 10.1159/000090342. Epub 2005 Dec 12.
Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus.
The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP.
Patients received a single dose of G-CSF (1 x 300 or 480 microg s.c.) prior to standard antibiotic treatment (n=8) or standard treatment only (n=8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessed using fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1 RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA.
In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6+/-9.7 vs. 71.2+/-17.7, p<0.01), neutrophil apoptosis decreased (apoptosis: 1.36+/-0.27 vs. 0.2+/-0.12%, p <.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4+/-72.2 vs. 340.1+/-194.6 ng/ml, p<0.01; sTNF-p55,382+/-4,243 vs. 632+/-4,714 ng/ml, p<0.01; control group nonsignificant). These effects were not seen in the control group.
The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.
尽管进行了抗生素治疗，但重症社区获得性肺炎（CAP）的死亡率，尤其是在伴有严重合并症的患者中，仍然很高。由细胞因子精心协调的包括多形核中性粒细胞（PMN）激活和存活在内的固有防御机制，主要负责从肺泡中清除细菌病原体。
本研究旨在评估粒细胞集落刺激因子（G-CSF）对CAP患者PMN激活、凋亡和细胞因子反应的影响。
患者在标准抗生素治疗前接受单剂量G-CSF（1×300或480μg皮下注射）（n = 8）或仅接受标准治疗（n = 8）。使用荧光激活细胞分选分析评估全身PMN上CD11b、CD66b、CD64和CD114表面分子的凋亡率和表达。通过酶联免疫吸附测定法测量白细胞介素-1受体拮抗剂（IL-1RA）、可溶性肿瘤坏死因子受体抑制剂（sTNF-p55）和G-CSF的水平。
在治疗组中，应用G-CSF后12小时，中性粒细胞计数增加，中性粒细胞激活标志物CD11b受到刺激（CD11b：48.6±9.7对71.2±17.7，p<0.01），中性粒细胞凋亡减少（凋亡：1.36±0.27对0.2±0.12%，p<.01），IL-1RA和sTNF-p55的浓度增加（IL-1RA 136.4±72.2对340.1±194.6 ng/ml，p<0.01；sTNF-p55，382±4,243对632±4,714 ng/ml，p<0.01；对照组无显著差异）。这些效应在对照组中未观察到。
在CAP患者中应用单剂量G-CSF可导致中性粒细胞存活时间延长、激活增加，并伴有抗炎细胞因子的持续释放。
