Jin Yang, Wan Yong, Chen Gang, Chen Long, Zhang Ming-Qiang, Deng Li, Zhang Jian-Chu, Xiong Xian-Zhi, Xin Jian-Bao
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Respiratory and Critical Care Medicine, Wuhan No. 1 Hospital, Wuhan, China.
PLoS One. 2014 Oct 16;9(10):e111044. doi: 10.1371/journal.pone.0111044. eCollection 2014.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systematic inflammation. An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes. T-helper (Th), T-cytotoxic (Tc) and T-regulatory (Treg) cells may play important roles in immune and inflammatory responses. This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD).
Twenty-three patients with stable COPD (SCOPD) and 21 patients with AECOPD were enrolled in the present study. In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls. The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies. Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of "inflammation adjustment" and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.
Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment. There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups. Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient. Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups.
These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions are strengthened, with the pro-inflammatory reactions dominating. Although the Treg/IL-17 ratios were normal, the regulatory T cells were still insufficient to suppress the accompanying increases in inflammation. All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated.
慢性阻塞性肺疾病（COPD）的特征为慢性肺部和全身性炎症。异常的适应性免疫反应导致促炎和抗炎过程失衡。辅助性T细胞（Th）、细胞毒性T细胞（Tc）和调节性T细胞（Treg）可能在免疫和炎症反应中发挥重要作用。本研究旨在阐明COPD患者，尤其是急性加重期（AECOPD）患者细胞因子和T淋巴细胞亚群的变化及失衡情况。
本研究纳入了23例稳定期COPD（SCOPD）患者和21例AECOPD患者。此外，纳入20名年龄、性别和体重匹配的非吸烟健康志愿者作为对照。使用酶联免疫吸附测定（ELISA）试剂盒检测所选细胞因子（转化生长因子-β、白细胞介素-10、肿瘤坏死因子-α、白细胞介素-17和白细胞介素-9）的血清水平。此外，用抗CD3-藻红蛋白（APC）、抗CD4-全藻青蛋白（PerCP）、抗CD8-PerCP、抗CD25-异硫氰酸荧光素（FITC）和抗叉头框蛋白3（FoxP3）-藻红蛋白（PE）单克隆抗体染色后，通过流式细胞术评估从外周血样本中收集的T淋巴细胞亚群。重要的是，为消除炎症因子的混杂影响，作者引入了“炎症校正”概念，并使用代表性炎症标志物（如肿瘤坏死因子-α和白细胞介素-17）校正每个测量值。
与其他细胞因子不同，无论是否校正，AECOPD患者的血清转化生长因子-β水平相对于对照组均显著升高。三组间CD4⁺或CD8⁺T细胞百分比无显著差异。虽然Treg在急性加重期相对上调，但其生成和分化能力仍远远不足。最后，作者指出各组间Treg/白细胞介素-17的比值相似。
这些观察结果表明，在COPD患者中，尤其是在急性加重期，促炎和抗炎反应均增强，且促炎反应占主导。虽然Treg/白细胞介素-17比值正常，但调节性T细胞仍不足以抑制伴随的炎症增加。所有这些变化提示促炎和抗炎失衡的机制复杂，有待进一步研究。
