IL-13: a promising therapeutic target for bronchial asthma

The incidence of allergic diseases has dramatically increased in recent decades, especially in urban and industrialized areas. It is important socially as well as medically to establish more useful strategies to overcome allergic disorders. Bronchial asthma is a complex disease characterized by airway inflammation involving a Th2-cytokine, interleukin (IL)-13. A substantial body of evidence has accumulated pointing to the pivotal role of IL-13 in the pathogenesis of bronchial asthma, based on mainly analyses of mouse models. In addition to such analyses, the high expression of IL-13 in lesions and genetic association of several genes coding IL-13 signaling molecules with bronchial asthma have raised the possibility that IL-13 plays a pivotal role in the onset or exacerbation of human bronchial asthma. Therefore, IL-13 and its signal pathway are thought to be promising targets to develop a therapeutic agent for bronchial asthma. In this article, we describe how IL-13 is involved in the pathogenesis of bronchial asthma and then how therapeutic agents to block IL-13 signals are developed for bronchial asthma.     

可溶性细胞间黏附分子-1与支气管哮喘病情程度的关系

目的探讨可溶性细胞间黏附分子－1（sICAM－1）与支气管哮喘发作及其病情严重程度的相关性。方法采用ELISA方法测定134例不同时期支气管哮喘患者及健康志愿者血清sICAM-1水平,同时对支气管哮喘急性发作期患者进行肺功能测定。结果63例急性发作期支气管哮喘患者血清sICAM-1[（298．05±52．33）ng／L]水平较缓解期患者[（213．36±16．88）．g／L]及健康志愿者[（117．83±13．23）ng／L]明显升高,并且随哮喘病情加重其值有明显升高;急性发作期患者肺功能第一秒用力呼吸量（FEV．％）值与血清slCAM-1呈明显负相关。结论slCAM-1是支气管哮喘发病中重要的黏附分子,可作为判断病情严重程度的指标之一。     

支气管哮喘患者外周血中IL-2﹑IL-4﹑IL-13和IgE的表达

目的：探讨哮喘患者外周血中IL-2、IL-4、IL-13和IgE的水平变化及临床意义。方法：抽取哮喘患者及正常对照组空腹静脉血2ml,采用双抗体夹心法（ELISA法）检测血清中IL-2、IL-4、IL-13和IgE的含量。结果：急性发作组和缓解组中IL-4、IL-13、IgE的含量明显高于正常对照组,差异有统计学意义（P〈0.01）,IL-2的含量低于正常对照组,差异具有统计学意义。急性发作组IL-4、IL-13、IgE高于缓解组,IL-2的含量低于缓解组,差异均具有统计学意义（P〈0.001）。结论：支气管哮喘患者外周血中IL-2、IL-4、IL-13和IgE水平的变化与支气管哮喘发病进程及临床诊治具有密切联系。     

Signal transduction by IL-2 and its receptors as target in treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and destructive arthropathy with systemic features, the etiopathogenesis of which remains unclear. It is characterized by relapsing and remitting inflammation and hyperplasia of synovial cells. Proinflammatory cytokines, such as interleukin-2 (IL-2), play an important role in maintaining cartilage damage and severe destruction of the joints due to an uncontrolled activation of cellular immunity. An imbalance between proinflammatory and anti-inflammatory mediators is likely to contribute to the chronicity of the disease. Therefore, insight into the activation state of T-cells in different stages of the disease may be important to understand pathogenetic mechanisms underlying RA and could be a lead for the design of future therapeutic strategies. Because of the central role of the IL-2/IL-2 receptor (IL-2R) system in mediation of the immune system, monitoring and manipulation of this system has important diagnostic and therapeutic implications. New approaches in RA therapy with anticytokine agents, which block cytokines and their receptors, are now used as antirheumatic drugs in clinical practice.     

血浆LL-37抗菌肽在支气管哮喘患儿发病中的作用研究

目的探究血浆LL-37抗菌肽、Ⅱ型肺泡细胞表面抗原(KL-6)、白三烯(LTS)在支气管哮喘患儿发病中的作用研究。方法选择2015年1月～2016年12月于我院诊断与治疗的72例哮喘患儿、60例非喘息性肺炎患儿为研究对象,分别设为哮喘组、肺炎组,同时选取相同年龄的60例正常儿童,设为对照组。采用酶联免疫吸附试验(ELISA)检测三组儿童血浆LL-37抗菌肽、KL-6以及LTS水平。检查各患儿肺活量(FVC)、第1秒用力呼气量(FEV1)以及FEV1%,并进行相关性分析。结果三组LL-37抗菌肽、KL-6、LTS水平差异有统计学意义(P<0.05),哮喘组血浆LL-37抗菌肽、KL-6、LTS水平显著高于肺炎组与对照组,肺炎组显著低于对照组,差异有统计学意义(P<0.05);三组FVC、FEV1、FEV1%差异有统计学意义(P<0.05),哮喘组FVC、FEV1、FEV1%显著低于肺炎组与对照组,肺炎组显著低于对照组,差异有统计学意义(P<0.05);血浆LL-37抗菌肽与FVC、FEV1、FEV1%呈负相关(P<0.05),血浆KL-6与FVC、FEV1、FEV1%呈负相关(P<0.05),血浆LTS与FVC、FEV1、FEV1%呈负相关(P=0.000)。结论哮喘患儿血浆LL-37抗菌肽、KL-6水以及LTS水平均显著高于非喘息性肺炎患儿及正常儿童,与肺功能呈负相关,提示LL-37抗菌肽、KL-6、LTS与哮喘的发病及发展密切相关。     

IL-17、IL-27和FeNO与支气管哮喘儿童肺功能的相关性及其对哮喘诊断的临床价值

目的 检测哮喘患儿白细胞介素-17(IL-17)、白细胞介素-27(IL-27)和呼出气一氧化氮(FeNO)水平的变化,探讨这些指标与肺功能指标的相关性、诊断哮喘的临床价值.方法 收集2019年5月—2020年5月在漯河市中心医院儿科接受治疗的64例哮喘患儿作为哮喘组,同期体检的30例健康儿童作为对照组.记录患者入院时...     

支气管哮喘的发病机制及药物治疗研究进展

支气管哮喘是一种慢性炎症引起的以气道高反应性和可逆性阻塞为特点的疾病。近年来随着对其发病机制的深入研究,尤其是对气道慢性炎症机制的全面了解,哮喘的治疗已取得很大进展。目前药物治疗是防治哮喘最有效的方法,应用广泛的药物有糖皮质激素、β2肾上腺素受体激动剂、茶碱类、M胆碱受体阻断药、过敏介质阻释药和抗白三烯药等。新型抗哮喘药物具有疗效好、不良反应少等特点,已成为研究的热点。     

The role of neurotrophins in bronchial asthma.

Allergic bronchial asthma is characterized by chronic inflammation of the airways, development of airway hyperreactivity and recurrent reversible airway obstruction. Target and effector cells responsible for airway hyperresponsiveness and airway obstruction include sensory and motor neurons as well as epithelial and smooth muscle cells. Although it is well established that the inflammatory process is controlled by T-helper (Th) 2 cells and the Th2-derived cytokines interleukin-4, airway hyperresponsiveness-5 and interleukin-13, the mechanisms by which immune cells interact with neurons, epithelial cells or smooth muscle cells still remain uncertain. Since there is growing evidence for extensive communication between neurons and immune cells, the mechanisms of this neuro-immune crosstalk in lung and airways of asthmatic patients are recently becoming the focus of asthma research. Neurotrophins represent candidate molecules regulating and controlling this crosstalk between the immune and peripheral nervous system. They are constitutively expressed by resident lung cells and produced in increasing concentrations by immune cells invading the airways under pathological conditions. They modify the functional activity of sensory and motor neurons, leading to enhanced and altered neuropeptide and tachykinin production. These effects are defined as "neuronal plasticity". The consequences are the development of "neurogenic inflammation" due to neuropeptide and tachykinin activities.     

白介素-13基因多态性与哮喘的相关性研究

目的探讨白介素-13(IL-13)基因多态性与哮喘的相关性。方法用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)方法检测96例汉族哮喘儿童及96名汉族健康儿童IL-13基因内含子区+1923位点的基因型和等位基因频率,分析此位点单核苷酸多态性与哮喘的易感性、血浆总IgE(TIgE)、IL-13水平的相关性。结果+1923位点等位基因C、T频率在两组间分布具有显著性差异(P<0.01),等位基因T与哮喘关联,OR(T/C)=1.87,95%CI=1.25～2.80,P<0.01。两组基因型(TT、CT、CC)频率的分布亦有显著性差异(P<0.01),哮喘组中TT、CT基因型人群外周血IL-13及TIgE水平与同组及对照组CC基因组比较有显著性差异(P<0.01)。结论 IL-13基因+1923位点多态性是影响哮喘的重要候选基因,T等位基因与哮喘关联,并可能通过增强IL-13基因的表达影响血浆总IgE水平。     

血清趋化因子CXCL13水平与支气管哮喘的相关性研究

目的 探讨血清C-X-C趋化因子13（CXCL13）水平与支气管哮喘不同疾病状态的相关性及其临床意义。方法 选取2015年1月至2016年4月安徽医科大学第一附属医院干部呼吸与危重症科诊断为支气管哮喘急性发作期患者32例（急性发作期组）,慢性持续期患者31例（慢性持续期组）为研究对象,并选取19例同期健康体检者为正常对照组纳入研究,检测3组研究对象血清CXCL13、免疫球蛋白E （IgE）、白细胞介素4（IL-4）、外周血嗜酸性粒细胞百分比（EOS%）,并比较其CXCL13的差异,分析急性发作期患者CXCL13、IgE、IL-4、EOS%之间的相关性;检测3组研究对象肺功能,分析急性发作期患者CXCL13水平与FVC%、FEV1%、FEV1/FVC之间的相关性。结果 支气管哮喘急性发作期组CXCL13、IgE、IL-4、EOS%水平高于慢性持续期组和正常对照组,差异均有统计学意义（P<0.05）;支气管哮喘急性发作期组血清CXCL13与IgE、IL-4及EOS%呈正相关（r=0.507、0.334、0.586,P<0.05）,与FEV1%呈负相关（r=-0.389,P<0.05）。结论 血清CXCL13可能在支气管哮喘的进程中发挥促炎作用。     

Roles of histamine in the pathogenesis of bronchial asthma and reevaluation of the clinical usefulness of antihistamines

Histamine has been reported to play an important role in pathogenesis of bronchial asthma. However, H1-blockers are not recommended as the first drug for asthma therapy in the guidelines. Histamine may play various roles in allergic airway inflammation through the H1 receptor (H1R), H2R, and H4R in immune cells including T lymphocytes and dendritic cells. We therefore evaluated its role in allergic airway inflammation with the use of histamine-deficient mice. The results suggested that histamine plays a role in the prevention of goblet cell hyperplasia. Organic cation transporter-3 (OCT-3) is thought to be a transporter of histamine. Polymorphism of OCT-3 {R120R (T/C)} was associated with the severity of asthma. Recently, it has been proposed that both asthma and allergic rhinitis should be treated as a single airway disease. Comorbidity of asthma and allergic rhinitis is very high (70-80%) and they share similar allergic inflammation. H1-blockers are recommended as first-line drugs to treat allergic rhinitis in the guidelines. Therefore H1-blockers are strongly recommended for patients with both asthma and allergic rhinitis.     

Effect of indomethacin in asthma: evidence against a role for prostaglandins in its pathogenesis.

1. A clinical trial of the effects of indomethacin (200 mg daily) failed to show any objective evidence of improvement in six patients. 2. The same dose failed to inhibit exercise and antigen challenge induced bronchoconstriction, and this was considered to be evidence against the hypothesis that prostaglandins act as chemical mediatros in the pathogenesis of asthma.     

The role of IL-17 and family members in the pathogenesis of arthritis

Interleukin (IL)-17 is a T-cell-derived cytokine that is expressed in the synovium of patients with arthritis. IL-17 contributes to the pathogenesis of arthritis, and demonstrates additive or even synergistic effects with IL-1 and tumor necrosis factor (TNF) in inducing joint pathology. It is a potent inducer of receptor activator of nuclear factor-kappa B. IL-17 also has the capacity to induce joint destruction in an IL-1-independent manner. The discovery of IL-17 family members may further elucidate the role of this cytokine family in arthritis pathology, with IL-17F a promising candidate. Anti-IL-17 cytokine therapy may be an interesting new antirheumatic approach to the prevention of joint destruction, in addition to anti-TNF and anti-IL-1 therapy.     

孟鲁司特对支气管哮喘患儿血清白细胞介素-17的影响

目的 探讨孟鲁司特对支气管哮喘患儿血清白细胞介素-17（IL-17）的影响.方法 90例支气管哮喘患儿随机分为两组,观察组50例,对照组40例,对照组采用常规治疗,观察组在常规治疗基础上加用孟鲁司特,治疗3个月后评价疗效,测定患儿治疗前后血清IL-17的变化.结果 观察组总有效率为96％,对照组总有效率为87.5％,两组比较差异有统计学意义（P＜0.05）.两组治疗后均明显降低血清IL-17的表达（P＜0.01）,并且与对照组比较,观察组降低更明显（P＜0.05）.结论 孟鲁司特可以通过拮抗IL-17而改善支气管哮喘患儿病情.     

支气管哮喘患者气道中白细胞介素-17表达与气道重塑关系的研究

目的初步探讨白细胞介素(IL)-17在支气管哮喘患者气道重塑中的作用。方法选取2007年9月至2008年9月门诊行气管镜检查的非急性发作期支气管哮喘患者40例,按肺功能测定结果分为2组。采用免疫组织化学方法分别检测其支气管肺泡灌洗液中肺泡巨噬细胞及气道上皮细胞的IL-17及转化生长因子(TGF)-β1的表达。采用方差分析和SNK-q检验进行统计学分析。结果支气管肺泡灌洗液肺泡巨噬细胞和气道上皮细胞中IL-17表达试验组分别为(0.361±0.190)和(0.306±0.014),较对照组[分别为(0.206±0.020)和(0.196±0.031)]明显升高,差异均有统计学意义(P<0.01);而TGF-β1表达试验组分别为(0.280±0.018)和(0.274±0.004),较对照组[分别为(0.206±0.006)和(0.193±0.015)]明显升高,差异均有统计学意义(P<0.01)。结论 IL-17可能在支气管哮喘气道重塑的发生发展中发挥作用。     

The eosinophil and its role in asthma

• 1.1. The eosinophil is part of the host defence mechanism to parasitic infection, but is also a key cell in many inflammatory disorders.
• 2.2. Eosinophils synthesise a range of pro-inflammatory and cytotoxic mediators, such as basic proteins, hydrolytic enzymes, lipid mediators, cytokines, oxygen metabolites and neuropeptides.
• 3.3. Eosinophils are recruited to the lung during episodes of asthma. They migrate from the blood vessels into the tissue via a series of interactions between their surface adhesion molecules and endothelial cells or the extracellular matrix.
• 4.4. Activation and prolonged survival of eosinophils occurs upon exposure to mediators released from other tissue resident leukocytes, including eosinophils themselves, and from respiratory tract epithelial cells. Release of eosinophilic mediators causes tissue damage and persistent inflammation of the lung.
• 5.5. Currently the most effective therapy for asthma lies with anti-inflammatory drugs, of which the main choices are inhaled corticosteroids or cromolyn sodium and nedocromil sodium.

     

支气管哮喘患者血清IL-33水平的变化及临床意义分析

目的 分析支气管哮喘患者血清IL-33水平的变化及临床意义。方法 选择本院收治的64例支气管哮喘患者为观察组,另选择同期于本院行健康体检的60例健康者为对照组,分别对两组对象的血清IL-33水平进行检测,并检测观察组患者的血清IgE及肺功能指标水平。对比和分析两组血清IL-33表达水平及观察组不同病情特点及严重程度的IgE及肺功能指标水平。结果 观察组的血清L-33水平高于对照组（P〈0.05）。观察组中急性发作期的血清L-33水平高于临床控制期（P〈0.05）,重度患者的血清L-33水平高于轻度和中度患者（P〈0.05）。观察组中急性发作期的血清IgE水平高于临床控制期（P〈0.05）,重度患者血清IgE水平高于轻度和中度患者（P〈0.05）。观察组中急性发作期的FEV1、FEV1/FVC、FEV1%pre均低于临床控制期（P〈0.05）,重度患者FEV1、FEV1/FVC、FEV1%pre均低于轻度和中度患者（P〈0.05）。观察组IL-33水平与IgE水平呈正相关（P〈0.05）,与FEV1、FEV1/FVC、FEV1%pre均呈负相关（P〈0.05）。结论 IL-33可能参与支气管哮喘的发生、发展,通过检测其水平变化有利于判断患者的肺功能及病情。     

成人支气管哮喘控制水平和影响因素分析

目的调查并研究影响成人支气管哮喘患者病情控制的危险因素。方法随机选取2016年7月至2017年6月期间我院收治56例支气管哮喘患者为探究对象,对这些患者的临床基本资料、治疗情况进行研究,并评估医生对患者哮喘水平的控制情况,对其具体的影响因素进行分析与研究。结果良好控制的患者(完全控制+部分控制)与未控制患者在患者超重、患有肥胖症、吸烟、酗酒、患有过敏性鼻炎、胃食管反流病、没有定期进行就诊等方面差异有统计学意义(P<0.05);而在文化教育程度以及家庭收入等方面差异无统计学意义(P>0.05)。全部哮喘患者当中,同时伴有超重、肥胖患者12例,占21%;伴有过敏性鼻炎患者14例,占25%;伴有胃食管反流病患者7例,占12%;伴有吸烟、酗酒16例,占29%;没有进行定期复诊的患者7例,占12%。所有影响因素对哮喘控制水平均有明显影响,差异有统计学意义(P<0.05)。结论本院对于成年支气管哮喘的病情控制水平有着严格的要求,只有将影响哮喘的具体因素进行控制,才能有效控制哮喘患者的病情,进而降低不良事件的发生,提升本院的医疗水平。     

The role of H2-receptors in bronchial reactivity in atopic asthma

The aim of the present study was to evaluate lung function and bronchial reactivity during therapy with the H2-blockers, cimetidine and ranitidine, in order to determine the role of H2-receptors in the bronchial response of asthmatic patients. Bronchial reactivity was evaluated by the histamine provocation test before, and 3 or 6 days after administration of cimetidine (800 mg per day) or ranitidine (300 mg per day). It was shown that after 6 days treatment, an increase in bronchial reactivity occurred in 85% of the patients treated with cimetidine and in 64% of the patients treated with ranitidine. These results seem to confirm the presence of H2 receptors in the bronchial tree of asthmatic patients. Blockade of these receptors causes an increase in bronchial reactivity and potential exacerbation of the asthmatic symptoms.     

长期吸入糖皮质激素对支气管哮喘患儿血清中瘦素、IL-13和IL-8水平的影响

目的观察支气管患儿血清中瘦素、IL-13和IL-8水平的变化并探讨长期吸入糖皮质激素后对支气管哮喘患儿血清中瘦素、IL-13和IL-8的影响。方法采用酶联免疫吸附（ELISA）的方法,分别检测70例支气管哮喘患儿采用吸入糖皮质激素治疗前,治疗3、6、12个月后及60例正常对照儿童血清中IL-13和IL-8水平;采用放射免疫法检测血清中瘦素浓度。结果支气管哮喘患儿血清中瘦素、IL-13和IL-8水平显著高于正常对照组。吸入糖皮质激素治疗3个月后支气管哮喘患儿血清中瘦素、IL-13和IL-8浓度与治疗前比较下降（P均〈0.05）,治疗6个月和12个月后显著低于治疗前（P均〈0.01）,且治疗12个月后各个炎症指标与对照组相比无显著性差异（P〉0.05）。结论长期吸入糖皮质激素是治疗儿童支气管哮喘的重要手段,其治疗作用与下调血清中瘦素、IL-13和IL-8水平有关。