Infection and Immunity Medical Investigation Unit, Hospital Clínico Universitario de Valladolid-IECSCYL, Valladolid, Spain.
Viral Immunol. 2012 Aug;25(4):249-53. doi: 10.1089/vim.2011.0095. Epub 2012 Jul 2.
The development of new diagnostic methods based on molecular biology has led to evidence of the important role of respiratory viruses in chronic obstructive pulmonary disease (COPD) exacerbations. Cytokines and chemokines are recognized as key actors in the pathogenesis of COPD. The objective of this study was to evaluate the association between viral infection and host cytokine responses in 57 COPD patients hospitalized with an acute exacerbation. Seventeen cytokines were profiled using a Luminex-Biorad multiplex assay in plasma samples collected in the first 24 h following hospital admission. Stepwise linear regression analysis was performed, taking into account the influence of seven potential confounding factors in the results. Twenty-four out of 57 showed radiological signs of community-acquired pneumonia (CAP) at hospital admission, 25 patients required admission to the intensive care unit (ICU), 20 had a bacterial infection, and 20 showed a detectable respiratory virus in pharyngeal swabs. Regression analysis showed that viral infection correlated with higher levels of interleukin-6 (IL-6) (log value of the coefficient of regression B, p=0.47, 0.044), and monocyte chemoattractant protein-1 (MCP-1) (p=0.43, 0.019), and increased admission to the ICU. Viral infection also correlated with higher levels of interferon-γ (IFN-γ) (p=0.70, 0.026), which, in turn, was inversely associated with the severity of illness. Finally, viral infection was independently associated with higher levels of tumor necrosis factor-α (TNF-α) (p=0.40, 0.002). Thus our study demonstrates that in patients with COPD exacerbations, viral infection is directly associated with higher systemic levels of cytokines central to the development of the antiviral response, which are also known to contribute to inflammation-mediated tissue damage. These results reveal a potential specific role of viral infection in the pathogenesis of COPD exacerbations.
基于分子生物学的新诊断方法的发展,使得呼吸道病毒在慢性阻塞性肺疾病(COPD)加重中起重要作用的证据得到了证实。细胞因子和趋化因子被认为是 COPD 发病机制的关键因素。本研究旨在评估 57 例因急性加重而住院的 COPD 患者的病毒感染与宿主细胞因子反应之间的相关性。在入院后 24 小时内采集的血浆样本中,使用 Luminex-Biorad 多重分析检测了 17 种细胞因子。采用逐步线性回归分析,考虑到结果中七个潜在混杂因素的影响。57 例患者中,24 例入院时出现社区获得性肺炎(CAP)的影像学征象,25 例需要入住重症监护病房(ICU),20 例有细菌感染,20 例咽拭子检测到呼吸道病毒。回归分析显示,病毒感染与白细胞介素-6(IL-6)(回归系数 B 的对数值,p=0.47,0.044)和单核细胞趋化蛋白-1(MCP-1)(p=0.43,0.019)水平升高相关,与入住 ICU 相关。病毒感染还与干扰素-γ(IFN-γ)(p=0.70,0.026)水平升高相关,而后者与疾病严重程度呈负相关。最后,病毒感染与肿瘤坏死因子-α(TNF-α)(p=0.40,0.002)水平升高独立相关。因此,我们的研究表明,在 COPD 加重的患者中,病毒感染与抗病毒反应的核心细胞因子的全身性水平升高直接相关,这些细胞因子也已知会导致炎症介导的组织损伤。这些结果揭示了病毒感染在 COPD 加重发病机制中的潜在特定作用。