哮喘患者痰液炎性标志物检测及意义

在哮喘炎症的发生,发展中,炎症细胞,介质和细胞因子等均起了重要作用,检测其在痰液中的水平对于阐明哮喘气道炎症机制,判断病情并指导治疗具有重要意义。     

白细胞介素18对灭活呼吸道合胞病毒诱导小鼠肺部嗜酸细胞炎症的抑制作用

支气管哮喘是多种炎症细胞参与的气道慢性非特异性炎症 ,其中浆细胞和嗜酸细胞 (ＥＯＳ)被认为在气道炎症反应中起重要作用。它们不仅能释放一系列炎症介质 (如Ｉ犂Ｅ和嗜酸细胞阳离子蛋白等 )加重哮喘气道炎症 ,而且会损伤气道上皮导致气道高反应性。故以浆细胞和ＥＯＳ浸润为主要病理变化的炎症反应 ,被认为是支气管哮喘的重要特征之一[1] 。白细胞介素 18(ＩＬ 18)是最近发现的一种免疫调节因子。目前有关它在支气管哮喘发病机制中的作用尚未明了。为探讨ＩＬ 18对支气管哮喘气道ＥＯＳ和浆细胞的作用 ,我们在小鼠哮喘模型上观察了ＩＬ 1…     

真菌引起支气管哮喘发展和加重的免疫学机制

支气管哮喘（简称哮喘）是常见的气道慢性炎症性疾病,多种环境因素可引起哮喘恶化加重,其中真菌感染是一个很重要的因素。有很多证据显示哮喘患者存在真菌致敏,且在真菌致敏和哮喘严重度之间存在强的相关性。近年来很多研究主要从真菌对免疫细胞和上皮细胞的影响两个方面阐释了真菌引起哮喘加重的免疫学机制。此免疫学机制的阐明对于探索治疗重症哮喘的新途径有重要的意义。     

真菌引起支气管哮喘发展和加重的免疫学机制

支气管哮喘(简称哮喘)是常见的气道慢性炎症性疾病,多种环境因素可引起哮喘恶化加重,其中真菌感染是一个很重要的因素.有很多证据显示哮喘患者存在真菌致敏,且在真菌致敏和哮喘严重度之间存在强的相关性.近年来很多研究主要从真菌对免疫细胞和上皮细胞的影响两个方面阐释了真菌引起哮喘加重的免疫学机制.此免疫学机制的阐明对于探索治疗重...     

中性粒细胞分泌功能与支气管哮喘

哮喘是由多种炎症细胞和炎症组分参与的气道慢性炎症。近年来发现中性粒细胞(PMN)在哮喘的发病机制中也起重要作用,尤其表现在重度哮喘和致命性哮喘中。激活的PMN能分泌多种酶、炎症介质和细胞因子等参与哮喘的发病过程。在此,对PMN分泌功能在哮喘中的作用作一综述。     

嗜酸粒细胞凋亡在支气管哮喘中的调控

嗜酸粒细胞（EOS）是哮喘炎症中的重要致炎细胞，EOS凋亡及其调控在哮喘发生，发展中起重要作用。本文从细胞，细胞因子，免疫分子及信号转导，基因调控等方面探论EOS凋亡的调控因素及机制。     

信号转导子和转录激活子6、过氧化物酶体增殖，活化体受体-γ与支气管哮喘

Th1／Th2细胞比例失调和Th2细胞优势分化是支气管哮喘发病的主要机制。信号转导子和转录激活子6（STAT6）是Th2细胞特异性转录因子，被IL-4等激活后诱导相关炎症基因的表达：STAT6信号通路在支气管哮喘气道炎症和高反应性中起重要作用。过氧化物酶体增殖活化体受体-γ（PPAR-γ）可通过抑制炎症信号通路，减轻气道炎症并抑制气道重构等。本文综述了STAT6在哮喘炎症中的作用及PPAR-γ对支气管哮喘炎症等方面的影响，为哮喘的临床治疗提供新的思路。     

呼吸道病毒感染与哮喘

呼吸道病毒感染引起哮喘急性发作的机制复杂，其中气道炎症的加重是核心机制。病毒引起的TH1型免疫反应可通过协助募集TH2细胞而加重哮喘气道炎症；病毒特异性CD8^-T细胞在某些条件下可发生表型转化，生成TH2型细胞因子；哮喘的慢性气道炎症也被认为可能与抗病毒免疫有关．因此呼吸道病毒感染除了加重哮喘外，还可能是哮喘慢性气道炎症和气道重塑的原因之一。     

重症支气管哮喘与真菌研究进展

近年大量证据提示，在支气管哮喘（哮喘）的诱发和加重危险因素中，吸人真菌过敏原是重症哮喘的重要诱因。真菌过敏原的直接暴露在哮喘的发生中起着非常重要的作用，现就严重的哮喘与真菌的相关联系进行综述。     

白介素—10与支气管哮喘的发病

哮喘是一种变态反应性炎症疾病，细胞因子在其发病机制中起着重要作用，其咩于抑制炎症作用的细胞因子的研究正引起人们的关注，白介素－１０具有广泛的抑制炎症的作用，本文综述哮喘发病过程中白介素－１０对细胞因子，细胞免疫，体液免疫等的调节作用。     

Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases.

Allergic bronchial asthma is a complex inflammatory diseases originated from dysregulated immune responses in the respiratory mucosa. The inflammatory state in asthmatic lung is characterized by massive infiltration with eosinophils, lymphocytes, and mast cells in the airway mucosa leading to airway hyperseisitivity, goblet cell hyperplasia and mucus overproduction. The inflammatory process is thought to be the result of intensive T helper (Th) 2-biased immune response. Over the past several years, there has been enormous progress in understanding the mechanisms for development of Th2-biased responses after inhaled exposure to allergens and the characteristics of CD4+ T cells prominently involved in this process. Recently, a new population of T cells, invariant natural killer T (iNKT) cells has been shown to play an important role in the pathogenesis of mouse model of allergic airway inflammation. iNKT cells are one of the most potent immune modulators through a massive production of a various cytokines including IL-4 and IFN-gamma upon activation, and are involved in a variety of immunoregulations including infection, autoimmunity, and tumor surveillance. The potent pathogenic role of iNKT cells in the development of bronchial asthma is due to their ability to produce predominant Th2 cytokines in a given condition. The involvement of iNKT cells in the pathogenesis of asthma might have been underestimated in the past studies demonstrating the involvement of CD4+ T cells in asthma because of the difficulty in the detection of iNKT cells. Meanwhile, growing evidences have demonstrated that iNKT cells could be a promising target for immune-based therapies for autoimmune diseases, tumor, and infection due to the invariance of their TCR usage, the restriction to the evolutionally-conserved non-polymorphic antigen-presenting molecule CD1d, and their outstanding ability to produce both Th1- and Th2-cytokines. In this review, we will overview current understanding of the pathophysiological roles of iNKT cells in asthma. We would also discuss on possible therapeutic approaches to bronchial asthma employing glycolipid ligands for iNKT cells.     

iNKT cells are increased in children with severe therapy-resistant asthma

Background

Invariant natural killer T (iNKT) cells play complex functions in the immune system, releasing both Th1 and Th2 cytokines. The role of iNKT cells in human asthma is still controversial and never described in severe therapy-resistant asthma in children. The objective of this work was to analyse iNKT frequency in peripheral blood of children with severe therapy-resistant asthma (STRA), compared to children with milder asthma and healthy controls.

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。     

血小板激活因子与支气管哮喘

支气管哮喘是由多种炎症细胞和炎症介质介导的慢性气道炎症。血小板激活因子（platelet-activating factot,PAF）是一种功能强大的脂类介质,主要和细胞膜上的PAF受体（PAF-Receptor,PAFR）结合介导生物学反应,在哮喘发生发展过程中具有重要意义。     

Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice

Obesity triggers a low-grade systemic inflammation, which plays an important role in the development of obesity-associated metabolic diseases. In searching for links between lipid accumulation and chronic inflammation, we examined invariant natural killer T (iNKT) cells, a subset of T lymphocytes that react with lipids and regulate inflammatory responses. We show that iNKT cells respond to dietary lipid excess and become activated before or at the time of tissue recruitment of inflammatory leukocytes, and that these cells progressively increase proinflammatory cytokine production in obese mice. Such iNKT cells skew other leukocytes toward proinflammatory cytokine production and induce an imbalanced proinflammatory cytokine environment in multiple tissues. Further, iNKT cell deficiency ameliorates tissue inflammation and provides protection against obesity-induced insulin resistance and hepatic steatosis. Conversely, chronic iNKT cell stimulation using a canonical iNKT cell agonist exacerbates tissue inflammation and obesity-associated metabolic disease. These findings place iNKT cells into the complex network linking lipid excess to inflammation in obesity and suggest new therapeutic avenues for obesity-associated metabolic disorders.     

Invariant natural killer T cells in chronic obstructive pulmonary disease

Background and objective: Invariant natural killer T (iNKT) cells may play an important role in regulating the innate and acquired immune systems in chronic obstructive pulmonary disease (COPD). However, there is little information regarding the potential role of iNKT cells in the pathogenesis of COPD. To investigate whether iNKT cells have an important role in COPD, the frequency of iNKT cells in peripheral blood of patients with COPD was analysed. Methods: This was a comparative study of 28 patients with COPD and 19 age‐matched healthy control subjects. Blood iNKT cells were stained with 6B11 mAb, anti‐T cell receptor Vα24 mAb, anti‐T cell receptor Vβ11 mAb or α‐galactosylceramide‐loaded CD1d‐tetramer, and analysed by flow cytometry. Results: The frequency of CD4⁺ 6B11⁺ iNKT, CD4⁺ Vα24⁺ iNKT, CD4⁺ Vβ11⁺ iNKT and CD3⁺ 6B11⁺ iNKT cells was significantly lower in peripheral blood of patients with COPD than in that of healthy control subjects. The frequency of CD4⁺ 6B11⁺ iNKT cells was significantly lower in patients with exacerbations of COPD compared with those with stable COPD. Conclusions: The frequency of iNKT was decreased in peripheral blood of patients with COPD. These results strongly suggest that iNKT cells may play an important role in the pathogenesis of COPD.     

Virus/Allergen Interactions in Asthma

Understanding the underlying mechanisms that cause and exacerbate allergic asthmatic disease is of great clinical interest. Clinical studies have revealed that allergies and viral respiratory illnesses are strongly linked to the inception and exacerbation of asthma, and suggest the possibility that there are interactive inflammatory mechanisms. Recent work has revealed a number of mechanisms of virus and allergen cross-talk that may play a role in the pathophysiology of allergic asthma, including (1) deficiency in virus-induced interferon responses, (2) defective epithelial barrier function, (3) increased release of epithelium-derived cytokines (e.g., thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, IL-33), (4) dysregulation of lymphocytes [e.g., innate lymphoid cells (ILCs), regulatory T cells (Tregs)], and (5) altered activation of purinergic receptors. One or more of these processes may provide targets for new therapeutics to treat allergic asthma and prevent disease exacerbation.     

New aspects of asthma.

It has now become apparent that asthma, even in its mildest clinical manifestation, is a chronic inflammatory condition of the airways. There have been important advances in understanding the special features of inflammation in asthmatic airways and the role of critical inflammatory cells such as mast cells (important in the acute inflammatory response) and eosinophils, macrophages and T-lymphocytes (involved in the chronic inflammatory response). Many inflammatory mediators have been implicated in asthma, and the development of mediator antagonists suggests that sulphidopeptide leukotrienes may play an important role in bronchoconstrictor responses. Cytokines released from many different cells in the airways are likely to be important in orchestrating and perpetuating the chronic inflammatory response. Chronic inflammation has effects on airway vessels, mucus secretion, smooth muscle and nerves, with evidence to suggest that there are structural changes which may lead to persistent airway abnormalities. The therapeutic implication of these new discoveries is that much earlier use of anti-inflammatory treatments (such as inhaled steroids) is preferable to reliance on bronchodilators which do not control the underlying inflammatory process.     

哮喘患者血PCT和IgE变化及其与病情的相关性

目的研究支气管哮喘患者血清降钙素原(PCT)、免疫球蛋白E(IgE)水平变化及其与患者病情相关性。方法对40例支气管哮喘患者(急性发作期组20例、缓解期组20例)、正常对照组20例健康受试者血清PCT、IgE水平进行检测,并分析PCT、IgE与第1秒用力呼气流量占预计值百分比(FEV1%)的相关性。结果急性发作期哮喘患者血清PCT和IgE均明显高于哮喘缓解期和健康对照组,差异具有统计学意义(P0.05);缓解期哮喘组血清PCT和IgE水平有所下降,但仍高于健康对照组,两组比较差异具有统计学意义(P0.05),支气管哮喘患者血清PCT和IgE均与FEV1%呈负相关(r=-0.314,P0.05和r=-0.587,P0.01)。结论支气管哮喘患者血清PCT和IgE处于高水平,而急性发作期升高程度更为显著,其变化与哮喘患者病情分期关系密切,能反映支气管哮喘患者的炎症反应和气道阻塞状态。     

Role of airway epithelial cells in development of asthma and allergic rhinitis

Asthma and allergic rhinitis frequently coexist in the same patient. There is a similarity and variation as well as potential relationship between asthma and allergic rhinitis. There is an increasing evidence to suggest a major involvement of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis. The present review describes the importance of the airway epithelial cell in the development of allergic airway diseases, its role as the primary airway defense against exposure of the airway and lung to inflammatory stimuli and antigens and as an important player through activation of epithelial Toll-like receptors (TLRs) to provide an important link between innate immunity and allergic disease. Additionally, airway epithelial cells can act as inflammatory promoters capable of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as active producers of several inflammatory/anti-inflammatory mediators. It is hypothesized that airway epithelial cells may play as both inflammatory initiator and immuno-pathological feedback regulation between allergic rhinitis and asthma via release of systemic inflammatory mediators. Thus, airway epithelial cells may be valuable therapeutic targets for discovery and development of new drugs and/or new therapeutic strategies to treat asthma and allergic rhinitis.