Kawayama Tomotaka, Kinoshita Takashi, Matsunaga Kazuko, Kobayashi Akihiro, Hayamizu Tomoyuki, Johnson Malcolm, Hoshino Tomoaki
Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Department of Respiratory Medicine, Fukuoka Sanno Hospital, Fukuoka, Japan.
Int J Chron Obstruct Pulmon Dis. 2016 Feb 10;11:295-303. doi: 10.2147/COPD.S95686. eCollection 2016.
To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC).
This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation.
In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α).
This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation.
比较日本慢性阻塞性肺疾病（COPD）患者、非COPD吸烟对照者及非COPD非吸烟对照者（NSC）细胞在体外刺激前后肺和全身炎症介质的释放情况。
这是一项非治疗性研究，每组10名受试者。在有或无脂多糖或肿瘤坏死因子（TNF）-α刺激的情况下，检测外周血单核细胞（PBMC）和痰液细胞中炎症生物标志物的释放，包括白细胞介素（IL）-6和-8、基质金属蛋白酶-9以及TNF-α。
在PBMC中，COPD组（81.6±111.4 pg/mL）和非吸烟对照者（9.5±5.2 pg/mL）之间基础TNF-α释放（均值±标准差）存在显著差异（P<0.05）。未观察到其他显著差异。刺激后生物标志物释放倾向于增加，COPD组变化最大。PBMC中脂多糖诱导的基质金属蛋白酶-9、TNF-α和IL-6释放的平均增加幅度最大。痰液样本刺激前后的数据比PBMC的数据更具变异性且结论性更差。在COPD组中，诱导痰液中性粒细胞水平高于两个对照组，巨噬细胞水平低于两个对照组。痰液细胞（巨噬细胞和中性粒细胞）数量与生物标志物水平（IL-8、IL-6和TNF-α）之间存在显著相关性。
这是第一项比较日本COPD患者、吸烟对照者和非吸烟对照者群体刺激前后细胞炎症介质释放情况的研究。COPD患者刺激后的水平往往更高。结果表明，COPD患者循环中的PBMC已预先激活。这进一步证明COPD是一种多成分疾病，涉及气道和全身炎症。
