白介素5与支气管哮喘

支气管哮喘是由多种细胞特别是嗜酸粒细胞、肥大细胞和T细胞参与的气道慢性过敏反应炎症性疾病。多种细胞因子参与哮喘的发生过程，其中白介素5（interleukin-5，IL-5）发挥了重要作用。本文就IL-5生物学功能、与哮喘的关系及其在哮喘的治疗前景等方面作一综述。     

三氧化二砷对支气管哮喘免疫及气道炎症的调控

支气管哮喘（简称哮喘）是一种由多种细胞（嗜酸粒细胞、T细胞、中性粒细胞、肥大细胞及肺泡上皮细胞等）及细胞组分参与的气道慢性炎症性疾病。三氧化二砷在动物实验中能改善哮喘小鼠的肺功能,在临床治疗中能使患者的哮喘症状得到长期控制。新近研究表明：三氧化二砷能明显抑制小鼠的体液免疫反应,抑制小鼠的肺、皮肤等组织的T细胞增殖,能下调IL-17、IL-18和IL-23等多种炎症因子的分泌,并且通过内质网应激途径诱导中性粒细胞凋亡,从而调节免疫,抑制炎症。文章综述了三氧化二砷调控哮喘免疫及气道炎症的最新研究进展,并进行了展望。     

Th2／Th17细胞群与支气管哮喘机制研究

支气管哮喘（简称哮喘）是一种由多种细胞（如嗜酸粒细胞、肥大细胞、T淋巴细胞、中性粒细胞和气道上皮细胞等）和细胞组分参与的气道慢性炎症性疾病。经典的Th1／Th2细胞失衡被认为是过敏性哮喘的主要发病机制,Th17／IL-17轴被证实与重症哮喘、激素抵抗型哮喘、以中性粒细胞浸润为主的哮喘有关。近年来研究发现,机体内存在一种不同于目前已知的Thl、Th2、Thl7、Th9等的新型CD4＋T细胞,被称为Th2／Th17双表型记忆性CD4＋T细胞群（简称Th2／Th17细胞群）。在哮喘发病机制的探讨中发现,Th2／Th17细胞群既能分泌Th2表型细胞因子IL-4、IL-5、IL-13,也可以分泌Th17型细胞因子IL-17、IL-8、IL-22等;且在不同的微环境下发生不一样的生物学效应,这显示了Th2／Th17细胞群可能在哮喘发生发展（特别是重症哮喘）及各亚型相互转化过程中起着决定性作用。现就Th2／Th17细胞群的生物学功能及其与哮喘的相关性进行如下综述。     

气道炎症、氧化应激反应标记物在哮喘患者中的应用

支气管哮喘（简称哮喘）是由多种细胞包括气道的炎症细胞和结构细胞（如嗜酸性粒细胞、肥大细胞、T淋巴细胞、中性粒细胞、平滑肌细胞、气道上皮细胞等）和细胞组分参与的气道慢性炎症性疾病^[1]。目前对该病的病因及发病机制尚未完全清楚,认为气道炎症和氧化应激在哮喘的发病中起着重要作用。     

肺泡巨噬细胞与支气管哮喘

支气管哮喘是一种由多种细胞参与的气道慢性炎症性疾病，其中包括气道的炎症细胞（嗜酸性粒细胞、淋巴细胞、肥大细胞、中性粒细胞、肺泡巨噬细胞、嗜碱性粒细胞等）和非炎症细胞（气道上皮细胞、平滑肌细胞等）。     

T细胞在哮喘免疫调节中的作用

哮喘是由T细胞、嗜酸粒细胞、肥大细胞等多种炎症细胞参与的气道慢性炎症性疾病,气道慢性炎症导致气道高反应性（AHR）的形成.其中Th2细胞通过分泌IL-4、IL-5、IL-9、IL-13等多种细胞因子在哮喘发病中起主要作用,而Th1分泌的IFN-γ抑制Th2的功能,近年来研究发现CD4^＋T细胞还包括多种具有调节功能的细胞群体并参与哮喘的免疫调节.另外,NKT细胞和CD8^＋T细胞在哮喘免疫调节中亦具有一定的作用.     

IL-17＋ T淋巴细胞在哮喘发病中的参与及表达

目的用卵白蛋白（OVA）建立小鼠哮喘模型,观察IL-17＋ T淋巴细胞在哮喘发病过程中的参与情况。方法 30只BALB/c雌性SPF级小鼠随机分为正常对照组（n=15）和哮喘模型组（n=15）;分离小鼠肺支气管肺泡灌洗液（BALF）,对BALF中细胞总数和分类计数;分离外周血的淋巴细胞,用流式细胞术检测胞内细胞因子IL-17的表达,从而测定小鼠中IL-17＋ T淋巴细胞的含量。结果哮喘模型组BALF中细胞总数和中性粒细胞、嗜酸性粒细胞、淋巴细胞百分率均高于对照组（P〈0.01）。病理观察可见哮喘模型组小鼠的气道炎症以中性粒细胞及嗜酸性粒细胞浸润为主,而对照组无此变化。哮喘模型组外周血中IL-17＋ T淋巴细胞含量较正常对照组升高（P〈0.01）。结论 IL-17＋ T淋巴细胞参与了哮喘发病过程,在哮喘急性发作的气道炎症中扮有重要作用。     

反义寡核苷酸技术的研究进展与哮喘气道重塑的治疗

哮喘是严重影响人体健康的慢性呼吸道炎症性疾病。普遍认为哮喘是由多种细胞（如：嗜酸性粒细胞、T细胞、肥大细胞、中性粒细胞等）和细胞组分参与的气道慢性炎症性疾病，以气道慢性嗜酸性粒细胞炎症、气道高反应性和气道重塑为特点。近年来，人们逐渐认识到仅仅用气道炎症不足以解释哮喘病的慢性进行性和难以根治性，对哮喘研究的热点集中到了气道重塑上。     

哮喘患者诱导痰中IL-17A、IL-8及MMP-9水平变化及糖皮质激素对其的影响

目的探讨哮喘患者气道炎症特点及糖皮质激素的作用机制。方法将33例哮喘患者（哮喘组）按病情程度分为轻、中度19例及重度14例,予规范吸入糖皮质激素治疗4周,行诱导痰炎性细胞分类并计数,采用ELISA法检测痰上清液炎性介质白细胞介素-17A（IL-17A）、IL-8、基质金属蛋白酶-9（MMP-9）水平,并与15例查体健康者（对照组）进行比较。对诱导痰细胞分类、1秒钟用力呼气量占预计值百分比（FEVl％）及炎性介质水平进行相关分析。结果重度哮喘者诱导痰中性粒细胞、嗜酸性粒细胞比值及上清液IL-17A、IL-8、MMP-9水平显著高于对照组及轻、中度者;轻-中度者除MMP-9无显著升高外,余各指标均显著高于对照组（P均〈0．01）。诱导痰中性粒细胞及嗜酸性粒细胞比值与FEV1％呈显著负相关;中性粒细胞比值与IL-8、MMP-9呈正相关;IL-17A水平与中性粒细胞比值、IL-8呈正相关。糖皮质激素治疗后重度者中性粒细胞、嗜酸性粒细胞比值及MMP-9水平仍显著高于轻-中度者。结论中性粒细胞浸润性气道炎症是重度持续性哮喘的重要特征;IL-17A、IL-8与MMP-9可能在其中发挥重要作用。吸入糖皮质激素能抑制炎症细胞的趋化效应,阻止炎症释放,稳定细胞溶酶体膜,减轻组织损伤。     

支气管哮喘的免疫治疗进展

支气管哮喘（简称哮喘）是由多种细胞（如嗜酸粒细胞、肥大细胞、T细胞、中性粒细胞、气道上皮细胞等）和细胞组分参与、以气道高反应为主要病理生理特征的气道慢性特殊性炎症性疾病。其病因与发病机制复杂。个体变应性体质及环境因素是其发病的主要危险因素,气道的变应性炎症是其发病的中心环节,免疫治疗是目前针对哮喘病因治疗的主要方法,本文就哮喘的免疫学机制和免疫治疗进行概述。     

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32在气道炎症反应中的研究进展

在哮喘和慢性阻塞性肺疾病中,气道炎症反应始终贯穿疾病的发生、发展及转归.目前已发现有众多细胞及因子参与气道炎症反应,而白介素32作为一种新发现的细胞因子,很多文献证明其在炎症反应中有不可取代的作用.白介素32主要存在于自然杀伤细胞、T细胞、上皮细胞及外周血的单核细胞中,在自然免疫及特殊免疫中均有重要地位.在炎症反应中,白介素32可诱导某些因子的活性,如白介素类、肿瘤坏死因子α、核因子、促分裂原活化蛋白激酶及各种趋化因子,形成炎症级联式反应,造成气道局部的炎症,甚至引起全身性炎症反应.本文对白介素32在气道炎症中的作用作一综述.     

Emerging mediators of airway smooth muscle dysfunction in asthma

Phenotypic changes in airway smooth muscle are integral to the pathophysiological changes that constitute asthma – namely inflammation, airway wall remodelling and bronchial hyperresponsiveness. In vitro and in vivo studies have shown that the proliferative, secretory and contractile functions of airway smooth muscle are dysfunctional in asthma. These functions can be modulated by various mediators whose levels are altered in asthma, derived from inflammatory cells or produced by airway smooth muscle itself. In this review, we describe the emerging roles of the CXC chemokines (GROs, IP-10), Th17-derived cytokines (IL-17, IL-22) and semaphorins, as well as the influence of viral infection on airway smooth muscle function, with a view to identifying new opportunities for therapeutic intervention in asthma.     

Lipopolysaccharides promote a shift from Th2-derived airway eosinophilic inflammation to Th17-derived neutrophilic inflammation in an ovalbumin-sensitized murine asthma model

Introduction: The currently available treatments for severe asthma are insufficient. Infiltration of neutrophils rather than eosinophils into the airways is an important inflammatory characteristic of severe asthma. However, the mechanism of the phenotypic change from eosinophilic to neutrophilic inflammation has not yet been fully elucidated. Methods: In the current study, we examined the effect of lipopolysaccharides (LPS) on eosinophilic asthmatic mice sensitized with ovalbumin (OVA), as well as the roles of interleukin (IL)-17A/T helper (Th) 17 cells on the change in the airway inflammatory phenotype from eosinophilic to neutrophilic inflammation in asthmatic lungs of IL-17A-deficient mice. Results: Following exposure of OVA-induced asthmatic mice to LPS, neutrophil-predominant airway inflammation rather than eosinophil-predominant inflammation was observed, with increases in airway hyperresponsiveness (AHR), the IL-17A level in bronchoalveolar lavage fluid (BALF) and Th17 cells in the spleen and in the pulmonary hilar lymph nodes. Moreover, the neutrophilic asthmatic mice showed decreased mucus production and Th2 cytokine levels (IL-4 and IL-5). In contrast, IL-17A knockout (KO) mice exhibited eosinophil-predominant lung inflammation, decreased AHR, mucus overproduction and increased Th2 cytokine levels and Th2 cells. Conclusion: These findings suggest that the eosinophilic inflammatory phenotype of asthmatic lungs switches to the neutrophilic phenotype following exposure to LPS. The change in the inflammatory phenotype is strongly correlated with the increases in IL-17A and Th17 cells.     

Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma

BackgroundAccumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma.MethodsTDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control.ResultsTDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment.ConclusionsOur data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.     

嗜酸粒细胞在气道激活机制中的研究进展

支气管哮喘是一种以嗜酸粒细胞（eosinophils,EOS）和肥大细胞浸润、气道高反应性为主要病理生理特征的慢性气道炎症,其中EOS在气道的激活对疾病的发生发展起着关键作用。气道中的EOS主要来源于外周血,极小部分来源于气道内的嗜酸粒细胞前体祖细胞,前者早在外周血中便在内皮细胞的作用下开始启动激活,之后气道上皮细胞通过表达细胞因子IL-3、IL-6、IL-8、RANTES及EOS重要的趋化因子eotaxin等趋化其向气道迁移。两种来源的EOS在气道的激活都是各种炎症细胞、细胞因子、趋化因子相互作用的结果 ：一方面,气道内的Th2细胞、Th1细胞、Th17细胞、肥大细胞等通过分泌IL-4、IL-5、IL-17等细胞因子促进EOS的激活;另一方面,各种细胞因子如PAF、IL-33、IL-7等也通过各种途径激活EOS并维持EOS的活性。本文就目前国内外关于EOS在气道激活机制的研究情况作一综述。     

嗜酸粒细胞在气道激活机制中的研究进展

支气管哮喘是一种以嗜酸粒细胞(eosinophils,EOS)和肥大细胞浸润、气道高反应性为主要病理生理特征的慢性气道炎症,其中EOS在气道的激活对疾病的发生发展起着关键作用.气道中的EOS主要来源于外周血,极小部分来源于气道内的嗜酸粒细胞前体祖细胞,前者早在外周血中便在内皮细胞的作用下开始启动激活,之后气道上皮细胞通...     

Airway inflammation in subjects with gastro-oesophageal reflux and gastro-oesophageal reflux-related asthma

STUDY OBJECTIVES: Asthma and gastro-oesophageal reflux (GER) are both characterized by airway inflammation. DESIGN: The purposes of this work were (i) to study airway inflammation in patients troubled by gastro-oesophageal reflux (GER) and GER associated with asthma, (ii) to ascertain whether GER can aggravate asthma by exacerbating the pre-existing airway inflammation and oxidative stress and (iii) to establish the validity of analysing breath condensate and induced sputum when studying the airways of subjects affected by GER. PATIENT S AND METHODS: We enrolled 14 patients affected by mild asthma associated with GER (40 +/-12 years), nine with mild but persistent asthma (39 +/- 13 years), eight with GER (35 +/- 11 years) and 17 healthy subjects (37 +/- 9 years). Sputum cell counts and concentrations of interleukin-4 (IL-4), IL-6 and 8-isoprostane were measured in breath condensate and supernatant. MEASUREMENTS AND RESULTS: GER-related asthma is characterized by an eosinophilic inflammation, as determined by elevated concentrations of IL-4 in breath condensate and sputum supernatant, and by sputum cell analysis. GER alone presents a neutrophilic pattern of inflammation when determined by elevated concentrations of IL-6 in sputum cell analysis. A concomitant increase has been found in 8-isoprostane in GER associated (or not associated) with asthma. CONCLUSIONS: We conclude that GER is characterized by a neutrophilic airway inflammation and by increased oxidative stress. GER does not however aggravate pre-existing airway inflammation in asthma patients. Determinations of inflammatory and oxidant markers in the breath condensate of subjects with GER reflect these measured in the induced sputum.     

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。     

三氧化二砷对支气管哮喘免疫及气道炎症的调控

支气管哮喘(简称哮喘)是一种由多种细胞(嗜酸粒细胞、T细胞、中性粒细胞、肥大细胞及肺泡上皮细胞等)及细胞组分参与的气道慢性炎症性疾病.三氧化二砷在动物实验中能改善哮喘小鼠的肺功能,在临床治疗中能使患者的哮喘症状得到长期控制.新近研究表明:三氧化二砷能明显抑制小鼠的体液免疫反应,抑制小鼠的肺、皮肤等组织的T细胞增殖,能下...