Andelid Kristina, Tengvall Sara, Andersson Anders, Levänen Bettina, Christenson Karin, Jirholt Pernilla, Åhrén Christina, Qvarfordt Ingemar, Ekberg-Jansson Ann, Lindén Anders
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Unit of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Int J Chron Obstruct Pulmon Dis. 2015 Mar 27;10:689-702. doi: 10.2147/COPD.S76273. eCollection 2015.
We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.
我们研究了在患有包括慢性支气管炎在内的阻塞性肺病的吸烟者（慢性阻塞性肺病合并慢性支气管炎，OPD-CB）中，经由白细胞介素（IL）-17和生长相关致癌基因-α（GRO-α）的全身细胞因子信号传导是否受损。我们还研究了这种全身细胞因子信号传导与OPD-CB吸烟者气道中细菌定植的关系。目前正在吸烟的OPD-CB患者（n = 60，对应慢性阻塞性肺疾病全球倡议组织[GOLD] I-IV期）在60周内的稳定期和病情加重期接受了反复的血液和痰液采样。我们对血液中的细胞因子蛋白浓度和痰液中的细菌生长进行了表征。无症状吸烟者（n = 10）和从不吸烟者（n = 10）作为对照组。在临床稳定期，与从不吸烟的对照组相比，OPD-CB患者中IL-17和GRO-α的蛋白浓度明显较低，而无症状吸烟者对照组则显示出中等浓度。值得注意的是，在OPD-CB患者中，与常见呼吸道病原体或口咽菌群定植相比，机会性病原体定植与明显较低的IL-17和GRO-α相关。在OPD-CB患者病情加重期间，GRO-α和中性粒细胞浓度增加，而IL-17的蛋白浓度和信使核糖核酸无法以可重复的方式检测到。在患有OPD-CB的吸烟者中，经由IL-17和GRO-α的全身细胞因子信号传导受损，这种改变可能与气道中机会性病原体的定植有关。鉴于其潜在的致病和治疗意义，这些发现值得在新的更大的患者队列中进行验证。
