In vivo application of Granulocyte-Macrophage Colony-stimulating Factor enhances postoperative qualitative monocytic function
In vivo application of Granulocyte-Macrophage Colony-stimulating Factor enhances postoperative qualitative monocytic function
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DOI：
10.7150/ijms.18288
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发表时间：
2017-01-01
影响因子：
3.6
通讯作者：
Spies, Claudia
中科院分区：
文献类型：
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作者：
Lachmann, Gunnar;Kurth, Johannes;Spies, Claudia
背景：粒细胞巨噬细胞集落刺激因子（GM-CSF）可作为免疫抑制患者的有效刺激剂，其定义为手术后单核细胞（mHLA-DR）上人白细胞抗原d相关表达减少。然而，GM-CSF对单核细胞和T细胞功能的确切作用尚不清楚。方法：回顾性随机对照试验（RCT）亚组分析20例食管或胰腺切除术后免疫抑制（即术后第一天每个细胞mHLA-DR水平低于10,000单克隆抗体（mAb））患者的单核细胞T细胞功能和T细胞亚种。如果mHLA-DR水平低于每个细胞10,000 mAb，每10名患者最多连续3天接受GM-CSF （250 μ g/m(2)/d）或安慰剂治疗。术前（od）至术后第5天（pod5）测量mHLA-DR及其他免疫功能参数。采用非参数统计程序进行统计分析。结果：在多因素分析中，mHLA-DR在两组间差异有统计学意义（p < 0.001）。GM-CSF应用后，mHLA-DR在pod2 （p < 0.001）和pod3 （p = 0.002）上升高。脂多糖（LPS）刺激单核细胞的肿瘤坏死因子- α (tnf - α)释放在两组间有显著差异（p < 0.008）， GM-CSF组在pod2 （p < 0.001）和pod3 （p = 0.046）上增加。GM-CSF对pod2处理后，Th17/调节性T （Treg）细胞比例升高（p = 0.041）。刀豆蛋白（Con） A刺激T细胞后，各组淋巴细胞和辅助性T细胞（Th）1/Th2特异性细胞因子的产生无差异。结论：术后应用GM-CSF后，LPS刺激后mHLA-DR和tnf - α释放增加，Th17/Treg比值明显提高，从而显著增强定性单核细胞功能。
BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) can be used as a potent stimulator for immune suppressed patients as defined by a decrease of human leukocyte antigen-D related expression on monocytes (mHLA-DR) after surgery. However, the exact role of GM-CSF on monocytic and T cell function is unclear. METHODS: In this retrospective randomized controlled trial (RCT) subgroup analysis, monocytic respectively T cell function and T cell subspecies of 20 immune suppressed (i.e. mHLA-DR levels below 10,000 monoclonal antibodies (mAb) per cell at the first day after surgery) patients after esophageal or pancreatic resection were analyzed. Each 10 patients received either GM-CSF (250 mu g/m(2)/d) or placebo for a maximum of three consecutive days if mHLA-DR levels remained below 10,000 mAb per cell. mHLA-DR and further parameters of immune function were measured preoperatively (od) until day 5 after surgery (pod5). Statistical analyses were performed using nonparametric statistical procedures. RESULTS: In multivariate analysis, mHLA-DR significantly differed between the groups (p < 0.001). mHLA-DR was increased on pod2 (p < 0.001) and pod3 (p = 0.002) after GM-CSF application. Tumor necrosis factor-alpha (TNF-alpha) release of lipopolysaccharide (LPS) stimulated monocytes multivariately significantly differed between the groups (p < 0.008) and was increased in the GM-CSF group on pod2 (p < 0.001) and pod3 (p = 0.046). Th17/regulatory T (Treg) cell ratio was higher after GM-CSF treatment on pod2 (p = 0.041). No differences were seen in lymphocytes and T helper cell (Th)1/Th2 specific cytokine production after T cell stimulation with Concanavalin (Con) A between the groups. CONCLUSIONS: Postoperative application of GM-CSF significantly enhanced qualitative monocytic function by increased mHLA-DR and TNF-alpha release after LPS stimulation and apparently enhanced Th17/Treg ratio.