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.     

炎症反应在慢性阻塞性肺疾病伴发肺动脉高压中的作用

炎症反应在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)伴发肺动脉高压的发生、发展中起着重要作用.气道存在炎症时,激活的炎症细胞释放肿瘤坏死因子a(TNF-α)、白介素6(IL-6)和IL-8等多种细胞因子,共同参与气道壁、肺泡壁的结构破坏和重塑.这些气道炎症反应不仅影响已存在缺氧的COPD伴肺动脉高压患者,也可影响尚不存在缺氧的COPD伴肺动脉高压患者,可能是早期COPD患者肺动脉重塑及血流动力学改变的始动环节.     

炎症在慢性阻塞性肺疾病相关肺动脉高压发病机制中的作用的研究进展

慢性阻塞性肺疾病(COPD)是以气道、肺实质、肺血管慢性炎症为主要特征的慢性肺疾病.肺动脉高压是COPD的主要并发症.近年来新的研究表明,COPD相关肺动脉高压的主要发病机制除缺氧外,炎症介质如白介素16、C反应蛋白、肿瘤坏死因子α、内皮素1等及炎症细胞如中性粒细胞、T淋巴细胞、巨噬细胞、肥大细胞等也起重要作用.     

神经营养素在慢性阻塞性肺疾病中的作用

气道结构细胞、炎性细胞通过自分泌或旁分泌神经营养素(NTs)参与气道高反应、气道炎症、气道重塑,在肺过敏性疾病及炎性疾病中发挥重要作用.目前,NTs及受体在慢性阻塞性肺疾病研究较少,但依然可以证实NTs及受体介导了气道炎症、气道神经源性炎症、气道重塑,从而参与慢性阻塞性肺疾病的发病机制.     

YKL-40(BRP-39)与支气管哮喘

支气管哮喘(简称哮喘)是一种由多种炎症细胞、炎症因子参与的慢性气道炎症性疾病,Th2分化过度在哮喘气道炎症中起重要作用.YKL-40(BRP-39)是新近发现的壳质酶类似物蛋白,参与多种疾病的炎症反应、组织结构重塑等病理过程.YKL-40可通过促进哮喘患者Th2活化、分化并减少其凋亡,增加Th2数量,在哮喘慢性气道炎症中起着重要作用.     

大环内酯类药物在慢性阻塞性肺疾病气道及肺部炎症中的作用

慢性阻塞性肺疾病（COPD）是一种以气流受限为特征的疾病，气流受限不完全可逆、呈进行性发展，与肺部对有害气体或有害颗粒的异常炎症反应有关.所以COPD的实质是肺部的异常炎症反应，其炎症特点为细胞毒性T细胞、单核细胞、中性粒细胞和巨噬细胞数量增多，且释放大量炎症介质，并有高水平的氧化应激，这进一步扩大这种慢性炎症;其炎症部位涉及气道、肺泡壁和肺血管，导致这些组织的功能结构异常，从而引起气流受限、肺气肿和肺动脉高压.所以抗炎治疗在COPD治疗中有重要作用.人们在探索抗炎药物在慢性气道炎症中的作用过程中，发现大环内酯类药物（MA）具有抗炎、免疫调节等作用，且对气道慢性炎症具有肯定的疗效.本文重点介绍MA的生物学特性和分类，抗炎作用及其相关机制，对COPD气道及肺血管炎症及重塑的作用。     

Toll样受体4与气道慢性炎症性疾病

气道慢性炎症性疾病如慢性阻塞性肺疾病、支气管哮喘等是在各种内外界刺激因素作用下由气道固有细胞、炎症细胞和炎症因子参与的非特异性炎症性疾病.迄今已发现11种Toll样受体(TLR),均为I型跨膜受体蛋白,广泛表达于支气管上皮细胞、支气管平滑肌细胞、树突状细胞、肺泡巨噬细胞等,因其能感知病原体并直接或间接作出防御反应而在慢性气道炎症性疾病的发生发展中发挥重要作用,其中又以TLR4的作用最为突出而成为研究的热点.故深入认识TLR4与慢性气道炎症性疾病的关系将为临床治疗开辟广阔的前景.     

血栓素A2与慢性肺部炎症性疾病

在慢性阻塞性肺疾病、支气管哮喘和肺囊性纤维化等气道慢性炎症性疾病中,常伴有广泛的气道结构破坏、重塑和黏液高分泌等病理改变.炎症介质血栓素A2(TXA2)是花生四烯酸的环氧合酶代谢产物之一,因其诱导血小板聚集、收缩血管及呼吸道平滑肌和刺激气道及血管平滑肌增殖而在这些病理改变中起着重要作用.TXA2作为一种重要的炎症介质,能刺激血管收缩,进而引起气道微血管渗漏,气道黏液增多,刺激气道平滑肌收缩进而引起气道阻力增加,并参与多种肺部炎症反应,近来还发现其可能参与杯状细胞化生和黏液分泌.现就其在肺部炎性疾病的作用作一综述.     

YKL-40（BRP-39）与支气管哮喘

支气管哮喘（简称哮喘）是-种由多种炎症细胞、炎症因子参与的慢性气道炎症性疾病,Th2分化过度在哮喘气道炎症中起重要作用。YKL40（BRP-39）是新近发现的壳质酶类似物蛋白,参与多种疾病的炎症反应、组织结构重塑等病理过程。YKL-40可通过促进哮喘患者Th2活化、分化并减少其凋亡,增加Th2数量,在哮喘慢性气道炎症中起着重要作用。     

慢性阻塞性肺疾病合并全身炎症反应综合征患者血清白介素-6、白介素-10和肿瘤坏死因子-α的变化

全身炎症反应综合征(SIRS)是由各种感染或非感染因素作用于机体而引起的一种全身性炎症反应,主要表现为全身高代谢状态和多种炎性介质的失控释放,最终可导致多器官功能障碍综合征(MODS)[1]慢性阻塞性肺疾病(COPD)是指具有不可逆气流受阻特征的疾病状态,通常是进行性发展,并伴有气道对毒性颗粒或气体的异常炎症反应有关的疾病.反复感染是加重气道炎症的主要原因之一.COPD急性加重时约80％患者达到全身炎症反应综合征(SIRS)的诊断标准[2].本研究通过检测COPD并SIRS患者血清白介素-6(IL-6)、白介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)的水平,探讨COPD并SIRS患者血清炎症因子水平的变化及其临床意义.     

炎性因子在慢性阻塞性肺疾病气道炎症中的作用

COPD是一种以气道慢性炎症为特征之一的慢性呼吸系统疾病,气道炎性反应在COPD占有重要作用。炎性细胞因子是机体内最重要的一类细胞因子,多种炎性细胞因子参与气道炎症的病理生理机制,对肺组织和支气管产生损害,并发肺外效应。在COPD的自然病程中存在炎性细胞因子网络系统,调控COPD的气道炎症的发生发展。     

Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells

CD8+ memory T cells have recently been recognized as playing a key role in natural immunity against unrelated viral infections, a phenomenon referred to as "heterologous antiviral immunity." We now provide data that the cellular immunological interactions that underlie such heterologous immunity can play an equally important role in regulating T helper 2 immune responses and protecting mucosal surfaces from allergen-induced inflammation. Our data show that CD8+ T cells, either retained in the lung after infection with influenza virus, or adoptively transferred via the intranasal route can suppress allergic airway inflammation. The suppression is mediated by IFN-gamma, which acts to reduce the activation level, T helper 2 cytokine production, airways hyperresponsiveness, and migration of allergen-specific CD4+ T cells into the lung, whereas the systemic and draining lymph node responses remain unchanged. Of note, adoptive transfer of previously activated transgenic CD8+ T cells conferred protection against allergic airway inflammation, even in the absence of specific-antigen. Airway resident CD8+ T cells produced IFN-gamma when directly exposed to conditioned media from activated dendritic cells or the proinflammatory cytokines IL-12 and IL-18. Taken together these data indicate that effector/memory CD8+ T cells present in the airways produce IFN-gamma after inflammatory stimuli, independent of specific-antigen, and as a consequence play a key role in modifying the degree and frequency of allergic responses in the lung.     

Bidirectional roles of IL-22 in the pathogenesis of allergic airway inflammation

Asthma is the most prevalent allergic disease of the airway, which is characterized by eosinophilic inflammation, mucus hyperproduction, and airway hyper-responsiveness. Although these pathognomonic features are mainly mediated by antigen-specific Th2 cells and their cytokines, such as IL-4, IL-5, and IL-13, recent studies have revealed that other inflammatory cells, including Th17 cells and innate lymphoid cells (ILCs), also play a critical role in the pathogenesis of asthma. IL-22, one of the cytokines produced by Th17 cells and type 3 ILCs, has distinct functional properties, as IL-22 exclusively acts on non-hematopoietic cells including epithelial cells of mucosal surface and exhibits a broad range of action in regeneration and host protection. In accordance with the fact that lung epithelial cells play a critical role in the pathogenesis of asthma, we and other groups have shown that IL-22 is involved in the regulation of allergic airway inflammation. In this review, we discuss recent advances in the biology of IL-22 and its involvement in the pathogenesis of allergic airway inflammation.     

白介素-10与炎症性肠病

炎症性肠病(inflammatory bowel disease,IBD)是一种慢性、复发性的肠道炎症疾病,其明确病因目前仍不清楚.肠道免疫功能异常导致过量炎症因子释放损伤肠道黏膜在IBD发病中起着关键作用,应用免疫抑制剂减少炎症因子的释放也被应用于IBD的治疗.近年来利用细胞因子调节机体免疫功能以治疗IBD的研究日渐...     

Regulation of inflammation by airway smooth muscle

Inflammatory mediators play a critical role in the pathogenesis of chronic airway diseases and facilitate the recruitment, activation, and trafficking of inflammatory cells in the airways. Compelling evidence now shows that airway smooth muscle expresses adhesion molecules and secretes inflammatory mediators. Airway myocytes also express a repertoire of immunomodulatory proteins such as Toll-like receptors, chemokines, and cytokines. The underlying mechanisms by which these molecules modulate airway inflammation and the physiological consequences of these molecules are now being elucidated, suggesting that airway smooth muscle plays an important role in orchestrating and perpetuating airway inflammation, remodeling, and fibrosis in chronic airway diseases.     

白介素17A及其在支气管哮喘中的作用

白介素17A（interleukin-17A,IL-17A）是近年来发现的一种由Th17等多种细胞产生的细胞因子,可以通过不同途径调节微环境中细胞因子、趋化因子、黏附性分子的表达,募集炎症细胞特别是中性粒细胞而发挥炎症效应,参与炎症性疾病。支气管哮喘（简称哮喘）是由多种炎症因子参与的慢性气道炎症性疾病,不断有证据表明IL-17A参与哮喘的发病过程。本文就IL-17A的来源及其在哮喘特别是中性粒细胞炎症性哮喘的气道炎症、气道高反应性、气道重塑及激素治疗抵抗中发挥的作用及机制加以综述。     

Le basophile humain et la réponse immunitaire

Allergic inflammation is the result of complex immune mechanisms that depends on cytokines produced by Th2 lymphocytes, which gives these cells a pivotal role in the allergic reaction. When activated by allergen, basophils produce IL-4 and IL-13, cytokines key in the allergic inflammatory response. Antigen activation induces expression of these two cytokines by basophils of only about 5–20% of allergic patients; basophils represent 80% of the IL-4 producing cells. Ionomycine can induce the production of these cytokines by basophils from most individuals, regardless of their clinical status. IL-4 production by basophils peaks at 2 h, whereas IL-13 expression is delayed, suggesting that basophils may be involved both in initiation and amplification of the allergic response. Furthermore, the rapid increase in CD40L expression on peripheral blood basophils suggests that they may be involved in IgE production. The CC chemokines increase the production of IL-4 by basophils, and stimulation with a 40-fold lower concentration of antigen then results in an equivalent level of IL-4 production. Diesel exhaust particles induce early IL-4 production by the majority of basophils, regardless of the individual’s allergic status; this effect is dependent on the generation of reactive oxygen species. Taken as a whole, these data add weight to the conclusion that basophils are involved in the pathophysiology of allergic diseases. In addition to their critical role in allergic inflammation, basophils may also be involved in anti-infectious immunity through the nonspecific mechanisms involved in innate immunity     

IL-21与COPD发病机制的研究进展

IL-21是近年来发现的一种细胞因子,主要由活化的 CD4+T 细胞产生,在 Th17细胞中大量分泌,IL-21与其受体结合后,参与免疫应答与炎症反应.COPD是一种由吸烟所诱发的 T 细胞介导的炎症及自身免疫性的疾病.COPD的发病机制复杂,其中免疫失衡在 COPD发生发展中起着重要作用,多种细胞因子的变化与 COPD有关,IL-21就是其中的一种.本文就 IL-21与 COPD 的气道炎症、肺气肿、肺动脉高压的发病机制的研究作一综述.     

上皮源性细胞因子与支气管哮喘

支气管哮喘(简称哮喘)是全球最常见的慢性气道炎症性疾病之一.慢性气道炎症是哮喘的内在发病机制,炎症细胞在气道的局部聚集、炎症介质和细胞因子的释放促使气道炎症发生.上皮源性细胞因子是免疫活性细胞的效应因子,其免疫调节功能在哮喘发病机制中处于中心地位.在人类肺组织及免疫细胞中,细胞因子的表达增高,从而导致肺部变态反应性疾病的发生.近年来利用哮喘发病机制中细胞因子作为靶点进行靶向治疗哮喘已成为未来哮喘治疗研究的主要热点.本文主要就上皮源性细胞因子中IL-25、IL-33及胸腺基质淋巴细胞生成素的结构和功能进行介绍,并对其与哮喘的关系作一简单综述.