白介素-8与慢性阻塞性肺疾病

白介素-8(IL-8)作为一种多源的细胞因子,主要作用于中性粒细胞。近来研究发现IL-8参与慢性阻塞性肺疾病(COPD)的发病,吸烟、感染均可诱导IL-8的产生。IL-8主要通过趋化、激活中性粒细胞和嗜酸粒细胞促进COPD的气道炎症反应。     

慢性阻塞性肺疾病患者血清白细胞介素—8水平的变化

白细胞介素-8(IL-8)是一种由多种细胞包括肺泡巨噬细胞、淋巴细胞、上皮细胞和嗜中性粒细胞(Neu)等产生的具有趋化活性的细胞因子,其主要作用是参与各种炎症过程中Neu的募集和活化。慢性阻塞性肺疾病(COPD)为支气管的慢性炎症。其特征为气流受阻及气道炎症细胞浸润。我们测定了COPD患者血清IL-8的水平,并与正常人作对照研     

辛伐他汀对老年COPD患者IL-17、IL-8及TNF-α水平的影响

<正>慢性炎症和进行性气流阻塞是慢性阻塞性肺疾病(COPD)的主要特征〔1〕。白细胞介素(IL)-17在COPD发病机制中具有重要作用。此外,IL-17能诱导IL-1β、肿瘤坏死因子(TNF)-α、IL-6、IL-8等因子的产生〔2〕,这些细胞因子又可趋化和调控中性粒细胞,从而导致中性粒细胞在气道内募集和激活,加重气道炎症。他汀类药物是当前最强效的降胆固醇药物,临床广泛应用于高脂血症、冠心病治疗等。近年发现他汀类药物除降脂     

老年慢性阻塞性肺疾病患者吸烟与肿瘤坏死因子-α介导全身炎症反应的关系

吸烟是慢性阻塞性肺疾病(COPD)的主要危险因素.长期吸烟引起气道炎症反应,表现为中性粒细胞、巨噬细胞、活化T细胞增生,细胞因子水平上升,包括肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和IL-8[1,2].虽然大多数吸烟者均显示有全身细胞和(或)体液炎症反应,仅少数人发生COPD[3],COPD患者全身炎症反应以中性粒细胞、巨噬细胞和T淋巴细胞数量增多,周围血中高浓度的炎症介质如C-反应蛋白(CRP)、IL-6、IL-8和TNF-α等[4～6].这些促炎因子主要由活化的巨噬细胞产生,在COPD的发病过程中起重要作用,最终导致组织损伤和重构[7].吸烟与COPD患者血浆TNF-α水平上升的确切机制尚不十分清楚[4,8].可溶性TNF受体升高,与全身TNF-α有关联的一种间接介质,能够影响COPD患者的全身炎症反应[9].本文探讨COPD患者吸烟与TNF-α介导全身炎症反应的关系.     

白细胞介素-17与慢性阻塞性肺疾病

白细胞介素(IL)-17是新发现的主要由CD4 记忆T淋巴细胞、单核细胞等分泌的一种前炎性细胞因子,具有强大的招募中性粒细胞、促进多种细胞释放炎性因子等多种生物学作用,参与呼吸道的炎症,从而在慢性阻塞性肺疾病(COPD)的发病机制中发挥重要作用.认识IL-17与COPD发病的关系有利于为临床治疗COPD提供新的治疗思路与药物.本文就IL-17在COPD中的作用进行综述.     

慢性阻塞性肺疾病炎症反应研究进展

目前研究显示气道炎症是慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)发病过程中的一个关键环节,中性粒细胞、淋巴细胞和肺泡巨噬细胞等多种炎症细胞和白三烯B4、白介素8、肿瘤坏死因子α、白介素6、基底细胞间黏附分子等多种炎症介质参与并影响气道炎症的发生.认识COPD炎症反应的特点和影响因素,能对COPD发生机制的探讨和临床治疗产生深远的影响.     

慢性阻塞性肺疾病血生物学标记物

COPD是一个以轻度慢性全身性炎症为特点的疾病,血液循环中存在多种炎性生物标志物,如中性粒细胞、C反应蛋白、纤维蛋白原、肿瘤坏死因子α、IL-6和IL-8等.基于这些炎性生物标志物的各种研究正逐步揭示着COPD的发病机制及病理生理过程.     

Th17细胞及其在慢性阻塞性肺疾病中的作用

最近研究发现一类不同于Th1和Th2的CD4+T细胞亚群-Th17细胞亚群.白介素6(IL-6)及转化生长因子β(TGF-β)是促进Th17分化的关键细胞因子.转录调节因子孤核受体是特异性调节Th17分化及功能的转录调节因子.目前慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的发病机制未明,慢性气道炎症特别是中性粒细胞的募集和激活被认为在COPD的发病中占有重要作用.Th17细胞通过其主要效应因子IL-17刺激IL-6、IL-8、粒巨噬细胞集落刺激因子及巨噬细胞炎性蛋白2等前炎症细胞因子招募中性粒细胞,同时促使气道黏液高分泌,调节气道重构,最终作用到相应的靶器官.随着Th17细胞研究的深入,有助于进一步阐明COPD的发病机制.     

慢性阻塞性肺疾病患者诱导痰IL-8、TNF-α水平和炎症细胞的分布

目的比较稳定期慢性阻塞性肺疾病（COPD）老年患者、老年健康吸烟者和老年健康非吸烟者痰液中IL-8、TNF-α水平和炎症细胞组成的差异,进而探讨IL-8、TNF-α、中性粒细胞与吸烟的相关性以及COPD气道炎症的性质。方法98例老年研究对象分为3组：COPD组38例、健康吸烟组（HS）30例、健康不吸烟组（HNS）30例,诱导痰方法收集痰液,细胞分类及计数,并用酶联免疫吸附法（ELISA）测定痰上清液中IL-8、TNF-α浓度。结果COPD组痰液中IL-8,、TNF-α、中性粒细胞百分比明显高于健康吸烟组及健康不吸烟组;COPD组痰液中IL-8、TNF-α水平与中性粒细胞百分比呈显著正相关性（r=0.761,r=0.495）;健康吸烟组痰中IL-8水平与中性粒细胞百分比亦呈显著正相关性（r=0.544）。结论IL-8和TNF-α和中性粒细胞共同参与了吸烟者COPD气道炎症反应。     

慢性阻塞性肺疾病患者痰液与外周血细胞分类、计数变化及意义

选择稳定期慢性阻塞性肺疾病(COPD)患者38例(COPD组),健康查体吸烟者29例(吸烟组)、不吸烟者18例(非吸烟组),分别测定其诱导痰和外周血细胞分类、计数.结果 与非吸烟组比较,COPD组诱导痰和外周血中嗜酸性粒细胞、CD8 T细胞明显增多,而巨噬细胞则显著减少;COPD组和吸烟组诱导痰中中性粒细胞明显增多.认为cOPD是由多种炎症细胞参与的气道炎症;CD8 T细胞可作为全身性炎症的标志物,有助于鉴别吸烟者是否存在COPD炎性改变.     

Nrf 2抗氧化系统在慢性阻塞性肺疾病中的作用

C O PD可致肺功能进行性减退,严重影响患者的生活质量,且目前为止尚无确切有效的治疗方法。尽管确切的病因仍不清楚,但是氧化应激被认为在疾病发病过程中扮演着重要角色。核因子相关因子2（Nrf2）是体内调节抗氧化系统的关键性转录因子之一,其目的基因表达的增加能增强细胞抗氧化作用。本文通过对氧化应激和 Nrf2介导的抗氧化系统,及其在COPD中的作用进行综述。     

Pathogenesis of COPD

Chronic obstructive pulmonary disease (COPD) is characterized and defined by limitation of expiratory airflow. This can result from several types of anatomical lesions, including loss of lung elastic recoil and fibrosis and narrowing of small airways. Inflammation, edema, and secretions also contribute variably to airflow limitation. Smoking can cause COPD through several mechanisms. First, smoke is a powerful inducer of an inflammatory response. Inflammatory mediators, including oxidants and proteases, are believed to play a major role in causing lung damage. Smoke can also alter lung repair responses in several ways. Inhibition of repair may lead to tissue destruction that characterizes emphysema, whereas abnormal repair can lead to the peribronchiolar fibrosis that causes airflow limitation in small airways. Genetic factors likely play a major role and probably account for much of the heterogeneity susceptibility to smoke and other factors. Many factors may play a role, but to date, only alpha-1 protease inhibitor deficiency has been unambiguously identified. Exposures other than cigarette smoke can contribute to the development of COPD. Inflammation of the lower respiratory tract that results from asthma or other chronic disorders may also contribute to the development of fixed airway obstruction. COPD is not only a disease of the lungs but is also a systemic inflammatory disorder. Muscular weakness, increased risk for atherosclerotic vascular disease, depression, osteoporosis, and abnormalities in fluids and electrolyte balance may all be consequences of COPD. Advances in understanding the pathogenesis of COPD have the potential for identifying new therapeutic targets that could alter the natural history of this devastating disorder.     

血管内皮生长因子在慢性阻塞性肺疾病中的作用

慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）由于日益增长的发病率和痫死率成为全世界主要的健康问题。但是,疾病的确切发病机制还没有被阐明。血管内皮生长因子（Vasculare ndothelial growth factor,VEGF）足血管形成的有效介质．对肺的发育和生理有多重作用。VEGF广泛存在于肺组织,对COPD的两种主要病理生理学表现型（肺气肿和慢性支气管炎）起了很重要的作用,观诵对临床的角度研究VEGF在COPD中的作用。     

Pathogenesis of COPD. Part III. Inflammation in COPD.

Chronic obstructive pulmonary disease (COPD) is mostly caused by cigarette smoking and affects up to 25% of smokers. Air pollution and occupational exposure to dust and fumes can also induce COPD. COPD is characterised by airflow limitation that is not fully reversible and chronic inflammation of the lung. Most patients with COPD also have evidence of tissue remodelling in the smaller airways. How the different pathological features are linked remains unknown. The inflammation of the COPD lung is initially caused by cigarette smoke and the increased infiltration of immune cells into the lung, but it is not clear why the inflammation persists after smoking cessation, while other pathologies partly reverse. Furthermore, anti-inflammatory treatments are not very successful and only control the symptoms but do not cure the disease. Animal models suggest that the imbalance of proteases and antiproteases is central to the major pathologies in the COPD lung. However, this hypothesis was never fully confirmed in humans and may only explain the degenerative stage of the disease, emphysema. The role of tissue-forming cells in the pathogenesis of COPD has not been adequately studied and indicates a deregulated synthesis of growth factors and cytokines in COPD. Finally, recent studies indicate that alpha-1-antitrypsin activity plays a role in all forms of COPD.     

中性粒细胞在慢性阻塞性肺疾病中的作用

慢性阻塞性肺疾病(chronic obstructive pneumonia discase,COPD)是以不完全可逆的气流受限为特征的慢性炎症性疾病.中性粒细胞可能在COPD的发展过程中发挥主要作用.活化的中性粒细胞释放蛋白酶、活性氧和细胞因子,引起肺组织损伤,最终导致气道黏液高分泌,气流受限和肺气肿.     

吸烟、肿瘤坏死因子及其受体与慢性阻塞性肺疾病

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)发病率高.发病机制不清.外界环境的刺激导致气道和血管损伤与修复的失平衡可能与COPD的发生相关.其中吸烟致细胞因子、炎症细胞及炎症介质增多,气道和肺实质慢性炎症,导致气道损伤和重构.最终导致气流受限,在肺气肿的形成中起主要作用.肿瘤坏死因子a是重要的炎症因子,通过其主要受体肿瘤坏死因子受体1参与COPD的形成,在COPD的发生、发展中起重要作用.     

The effect of inhaled corticosteroids on bronchoalveolar lavage cells and IL-8 levels in stable COPD patients

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammatory process in the large and small airways, as well as in the lung parenchyma. Although the role of oral corticosteroids in the management of acute exacerbations of COPD is well documented, its role in stable COPD is not clear. We examined the anti-inflammatory effect of inhaled budesonide on the percentage of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL) and their correlation with spirometry and symptom scores. Twenty-six patients with stable COPD were randomised, in a double-blinded, placebo-controlled trial with either 800 microg of inhaled budesonide or placebo for a 6-month period. The budesonide-treated subjects had significant reductions in IL-8 levels in the BAL after therapy (mean+/-sem, 1.53+/-0.72 at baseline vs. 0.70+/-0.48 ng/ml at 6 months, P=0.004) and a reduction in the mean percentages of neutrophils (17.16+/-2.67% vs. 13.25+/-2.28% P=0.002). The improvement in sputum production was of borderline (P=0.058) significance but there was no improvement in lung function. In stable patients with COPD, treatment with inhaled budesonide for a period of 6 months has a positive effect on markers of lung inflammation, as assessed by reduction in percentage neutrophils and IL-8 concentration in BAL.     

Pulmonary vasculature in COPD: The silent component

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that results from an inflammatory process affecting the airways and lung parenchyma. Despite major abnormalities taking place in bronchial and alveolar structures, changes in pulmonary vessels also represent an important component of the disease. Alterations in vessel structure are highly prevalent and abnormalities in their function impair gas exchange and may result in pulmonary hypertension (PH), an important complication of the disease associated with reduced survival and worse clinical course. The prevalence of PH is high in COPD, particularly in advanced stages, although it remains of mild to moderate severity in the majority of cases. Endothelial dysfunction, with imbalance between vasodilator/vasoconstrictive mediators, is a key determinant of changes taking place in pulmonary vasculature in COPD. Cigarette smoke products may perturb endothelial cells and play a critical role in initiating vascular changes. The concurrence of inflammation, hypoxia and emphysema further contributes to vascular damage and to the development of PH. The use of drugs that target endothelium‐dependent signalling pathways, currently employed in pulmonary arterial hypertension, is discouraged in COPD due to the lack of efficacy observed in randomized clinical trials and because there is compelling evidence indicating that these drugs may worsen pulmonary gas exchange. The subgroup of patients with severe PH should be ideally managed in centres with expertise in both PH and chronic lung diseases because alterations of pulmonary vasculature might resemble those observed in pulmonary arterial hypertension. Because this condition entails poor prognosis, it warrants specialist treatment.     

Functional significance of apoptosis in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a highly prevalent airway disease characterized by an abnormal inflammatory response of the lungs to noxious particles and gases. Cigarette smoking remains a major risk factor in COPD development. Accumulating evidence suggests that apoptosis, a regulated form of cell death, may play an important role in COPD pathogenesis. Increased numbers of apoptotic cells can be detected in lung tissue and airways of human subjects with COPD, relative to normal lungs or those from smokers without COPD. Alveolar wall destruction associated with emphysema development, may involve increased apoptosis of alveolar structural cells. Several intervention-induced apoptotic models (e.g., cigarette smoke, vascular-endothelial growth factor inhibition, and interferon-gamma) cause emphysematous changes in vitro and in vivo. Increased apoptosis in COPD can also imply defects in the normal physiological clearance of apoptotic cells. Additional factors that relate to perpetuation of the pathogenesis of COPD, including protease/antiprotease imbalance, inflammation and oxidative stress, may mutually promote apoptosis or contribute to impaired clearance of apoptotic cells. Given that cigarette smoking is the most common cause of COPD, identification of the pathways of cigarette smoke-induced apoptosis may further the understanding of COPD pathogenesis. However, apoptosis rate is not diminished after cessation of cigarette smoking, indicating that other mechanisms perpetuate apoptosis in COPD. Therefore, understanding functional relationships between apoptosis and protease/antiprotease imbalance, inflammation, oxidative stress and other factors potentially involved in COPD pathogenesis may uncover crucial therapeutic targets.     

The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD

COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe–COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe–host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.