嗜酸性粒细胞募集在支气管哮喘发病中的作用

支气管哮喘是一种气道慢性炎症性疾病,伴有嗜酸性粒细胞增多、杯状细胞肥大、黏液分泌增多、可逆性的气道阻塞及对吸入变应原和非特异性刺激的高反应性等特点,其中嗜酸性粒细胞募集和随后的激活在支气管哮喘发病中起着十分重要的作用。本文就嗜酸性粒细胞募集在支气管哮喘发病机制中的研究进展作一综述,为支气管哮喘的治疗提供一线新的曙光。     

IL—13在哮喘中的作用

支气管哮喘是以Th2型细胞因子增高和气道高反应性为特征的变态反应性疾病。白细胞介素-13(IL-13)是近年来新克隆的Th2型细胞因子，它通过诱导B细胞增殖和分化，促进IgE合成，活化嗜酸性粒细胞，延长嗜酸性粒细胞的存活，诱导气道高反应性等机制，在哮喘的发生中起重要的作用。     

嗜酸性粒细胞活化趋化因子与支气管哮喘的研究进展

嗜酸性粒细胞活化趋化因子(Eotaxin)是CC趋化因子家族成员之一,由结构性细胞和渗出性炎症细胞产生,是嗜酸性粒细胞、嗜碱性粒细胞和Th2型细胞因子的化学激活趋化剂,通过其受体(CCR3)选择性地诱导嗜酸性粒细胞在肺内黏附、募集和脱颗粒。     

I—4在支气管哮喘发病中的作用研究

研究ＩＬ－４在促使支气管哮喘发病中的作用。方法用ＥＬＩＳＡ方法检测３９例支气管哮产妇和４６例正常产妇新生儿脐血中ＩＬ－４、ＩＦＮ－γ,ｓＩＬ－２Ｒ和总ＩｇＥ含量,并计数脐血嗜碱性粒细胞数,同时用免疫磁珠纯化脐血Ｔ淋巴细胞和嗜碱性粒细胞,以ＲＴ－ＰＣＲ和ＥＬＩＳＡ方法检测上述细胞刺激后表达ＩＬ－４ｍＲＮＡ和ＩＦＮ－γｍＲＮＡ以及其释放的蛋白质。结果哮喘脐血组ＩＬ－４、ＩＮＦ－γ和ｓＩＬ－２Ｒ含量和哮     

IL—13与支气管哮喘

支气管哮喘是由多种细胞特别是肥大细胞、嗜酸性粒细胞和T淋巴细胞参与的慢性气道炎症。哮喘的发生过程中有多种细胞因子参与,白介素－13（IL－13）是近年来新克隆的淋巴因子。IL－13作为Th2型细胞因子成员,具有多种撑功能,通过激活嗜酸性粒细胞,减少其凋亡,促进IgE分泌等机制,参与哮喘炎症的维持,诱导气道高反应性及小气道结构重建。     

嗜酸性粒细胞阳离子蛋白在支气管哮喘中的研究

嗜酸性粒细胞阳离子蛋白(ECP)是活化嗜酸性细胞释放的强碱性蛋白中的重要组分,是嗜酸性粒细胞活化的重要标志,本文概述了ECP的来源,生物学作用以及与感染的关系,着重综述了ECP与支气管哮喘之间的关系。     

白介素13在哮喘发病机制中的作用

Th2淋巴细胞的优势应答及其释放的细胞因子被认为在哮喘的发病过程中起关键性作用。IL-13可不依赖于其它Th2型细胞因子及嗜酸粒细胞、Ig-E介导的途径而单独诱发哮喘的所有症状。IL-13基因多态性与哮喘的易感性也密切相关。其拮抗剂的应用有望成为哮喘病防治的新方法。     

支气管哮喘患者白细胞介素-4、13检测的临床意义

目的 探讨哮喘患者外周血白细胞介素-4（IL-4）和白细胞介素-13（IL-13）的变化及其在哮喘发病机制中的作用。方法 采用ELISA法检测30例支气管哮喘患者及25例正常对照组的血浆IL-13的含量。结果 支气管哮喘急性期患者的血浆IL-4、IL-13均明显高于正常对照组（P均〈0。01）。结论 IL-4、IL-13等因子多与支气管哮喘发病的病理生理过程，可为判断病情提供较好的实验室参数。     

白细胞介素-18对支气管哮喘小鼠气道炎症和核转录因子κB的作用

目的　探讨白细胞介素 18(IL 18)对支气管哮喘 (哮喘 )小鼠气道炎症及核转录因子κB(NF κB)的影响。方法　BALB c小鼠随机分为正常对照组 (A组 ,10只 )、哮喘模型组 (B组 ,10只 )、IL 18注射组 (C组 ,10只 )。B组和C组用经紫外线灭活的呼吸道合胞病毒 (RSV)激发法建立小鼠哮喘模型 ,分别于 1、2、7、8、9、2 1、2 2d腹腔注射生理盐水 (0 .1ml)和IL 18(1μg)。第 2 3天用HE染色切片观察动物气道炎症细胞的改变 ,用免疫组化和蛋白质定量分析法 (Westernblot)测定肺组织中NF κB的活性。结果　B组小鼠哮喘发作症状最明显 ,C组小鼠仅表现为轻度哮喘发作症状 ,A组小鼠无症状。A组支气管粘膜下未见嗜酸性粒细胞 (EOS)和浆细胞 ,B组支气管粘膜下可见EOS[15± 3(平均每视野计数 ,下同 ) ]和浆细胞 (10± 2 ) ,C组支气管粘膜下EOS(6± 2 )和浆细胞 (2± 1)较B组减少 (P<0 .0 5 )。肺组织冰冻切片免疫组化染色发现 :B组NF κB核表达最强 ,C组表达较弱 ,A组无表达。NF κB的抑制蛋白 (IκB)的Westernblot定量分析发现 :A组、C组的IκB含量分别是B组的 3.5和 2 .5倍 ,即说明B组NF κB的含量明显高于其他两组。结论　IL 18对支气管哮喘气道炎症有抑制作用 ,其机制之一可能与IL 18抑制了支气管哮喘小鼠肺组织中NF κ     

L-4在支气管哮喘发病中的作用研究

目的　研究IL 4在促使支气管哮喘发病中的作用。方法　用ELISA方法检测 39例支气管哮喘产妇和 46例正常产妇新生儿脐血中IL 4、IFN γ、sIL 2R和总IgE含量 ,并计数脐血嗜碱性粒细胞数 ,同时用免疫磁珠纯化脐血T淋巴细胞和嗜碱性粒细胞 ,以RT PCR和ELISA方法检测上述细胞刺激后表达IL 4mRNA和IFN γmRNA以及其释放的蛋白质。结果　哮喘脐血组IL 4、IFN γ和sIL 2R含量和嗜碱性粒细胞数虽高于正常脐血组 ,但两组差异无显著性 (P >0 .0 5 )。而纯化的脐血嗜碱性粒细胞表达IL 4mRNA和释放IL 4的水平 ,哮喘组显著高于正常脐血组 ,也高于T淋巴细胞。结论具有支气管哮喘遗传背景的新生儿脐血嗜碱性粒细胞对环境因素的刺激更加敏感 ,其释放的IL 4在促使支气管哮喘发病中起重要作用     

IL-13和IL-4在哮喘发病中的作用及相互关系

目的　探讨IL 13在哮喘发病中的作用及其与IL 4的相互关系。方法　哮喘组 2 4例 ,男 17例 ,女 7例 ;健康对照组 2 4例 ,男 12例 ,女 12例。用ELISA法检测不同时段PBMC培养上清IL 13和IL 4水平及加IL 13单克隆抗体 (McAb)和IL 4McAb干预后PBMC培养上清IL 4、IL 12、IL 13和IFN γ水平。结果　 (1)IL 13动态变化 :①对照组PBMC培养 3d、5d、7d水平均较培养 1d水平高 ,差异有显著性 ,培养 3d的水平较培养 5d、7d的高 ,差异有显著性 ;②哮喘组PBMC培养 3d、5d、7d的水平均较培养 1d的水平高 ,差异有显著性 ,培养 5d的水平均较培养 3d、7d的水平高 ,但之间差异无显著性 ;③哮喘组PBMC培养 3d、5d、7d的IL 13水平均较对照组高 ,差异有显著性。 (2 )IL 4动态变化 :①对照组和哮喘组PBMC培养 1d后 ,IL 4水平明显上升 ,第 3天仍保持较高水平 ,第 5、7天明显下降 ;②哮喘组 1d、3d、5d和 7d水平均较对照组高 ,差异有显著性。 (3)IL 4McAb干预后 ,哮喘组和正常组IL 13水平与对应小鼠IgG组相比有显著性降低 ,哮喘组IFN γ水平与对应小鼠IgG组相比有显著性增高。 (4)IL 13McAb干预后IL 12水平在哮喘组和正常组均提高 ,与对应小鼠IgG组相比差异有显著性。 (5 )IL 13McAb和IL 4McAb联合干预后哮喘组I     

Commonality of the IL-4/IL-13 pathway in atopic diseases

Introduction: Allergy results from an aberrant Type 2 inflammatory response, triggered by a wide range of environmental antigens (allergens) that lead to various immune responses, culminating in the production of immunoglobulin E (IgE). Two key cytokines, interleukin (IL)-4 and IL-13, are critical to the induction and perpetuation of the Type 2 response, and have been implicated in multiple atopic diseases.

Area covered: This review summarizes recent milestone developments that have elucidated components of the pathogenesis of atopic diseases such as atopic dermatitis (AD), asthma, and chronic sinusitis with nasal polyposis (CSwNP).

Expert commentary: Several therapeutic agents that selectively target potentiators of the Type 2 pathway have shown efficacy in one or more of these atopic diseases, but few agents have proven to be broadly applicable across all three atopic diseases. Dupilumab, a human monoclonal antibody that simultaneously inhibits signaling of IL-4 and IL-13, has demonstrated significant clinical efficacy in AD, asthma, and CSwNP. The fact that these diseases often occur as comorbidities and respond to the same therapy suggests that there is a common underlying pathogenic pathway, and that IL-4 and IL-13 cytokines are central to regulating the pathogenesis of these atopic diseases.     

eotaxin-3基因多态性与变应性哮喘的相关性

目的研究eotaxin-3基因多态性与变应性哮喘的相关性。方法用聚合酶链反应-单链构象多态性-四引物聚合酶链反应-限制性酶切的方法对湖北地区汉族成人eotaxin-3＋77C／T和＋2497T／G单核苷酸多态性与哮喘易感性、嗜酸性粒细胞（eosinophil，EOS）计数以及血浆总IgE水平的相关性进行了分析。结果eotaxin-3＋2497位哮喘组与对照组G等位基因的频率，哮喘组IgE浓度及EOS数量差异有统计学意义，P值分别为0．01l、0．021和0．029；＋77位哮喘组与对照组T等位基因的频率，哮喘组IgE浓度差异无统计学意义，P值分别为0．824和0．473；＋77位哮喘组EOS数量差异有统计学意义，P值为0．044。结论eotaxin-3＋2497T／G多态性与哮喘易感性、EOS数量及IgE水平相关，＋77位C／T基因多态性与哮喘EOS数量相关。     

IL-5 expression in the sputum of patients with bronchial asthma

Expression of IL-5 mRNA and the content of IL-5 in the sputum of patients with asthma of different severity were studied before and after treatment. The expression of IL-5 mRNA in mild asthma differed from that in severe and moderate asthma before and after treatment. The level of IL-5 before therapy was different in patients with mild and severe disease. In patients with severe asthma the level of IL-5 differed before and after treatment.     

The role of IL-13 in IgE synthesis by allergic asthma patients

IgE antibodies play a crucial role in allergic type I reactions. Only IL-4 and IL-13 are able to induce an immunoglobulin isotype switch to IgE in B cells. A major question is to what extent these cytokines contribute to the production of IgE in allergic patients. To address this question we used an in vitro culture system in which the production of IgE is dependent on endogenously produced IL-4 and IL-13. In cultures of purified T and B cells from allergic asthma patients and non-atopic controls, T cells were polyclonally stimulated to obtain IL-4, IL-13 and subsequently IgE secretion. The absolute amount of IgE produced was not significantly different between patients and controls. When neutralizing IL-4 antibodies were included during culture, the production of IgE was dramatically inhibited in both patients and controls (production of IgE was reduced to 12%). However, neutralization of IL-13 led to a significantly stronger inhibition of IgE production in the patient group: production of IgE was reduced to 23 ± 3% versus 50 ± 10% in the control group. Corresponding with these results, we also observed a higher production of IL-13 by the patients, while the production of IL-4 was not significantly different. A more detailed analysis of the production of IL-13 revealed that patients' T cells were less sensitive to a negative signal controlling IL-13 production. Our results indicate that, at least in vitro, IgE production in allergic asthma patients is more dependent on IL-13 than in non-atopics, due to enhanced IL-13 production and to enhanced IgE production in response to IL-13.     

Interleukin (IL)-4 and to a lesser extent either IL-13 or interferon-gamma regulate the production of eotaxin-2/CCL24 in nasal polyps

BACKGROUND: Eotaxin-2/CCL24 is a potent eosinophil attractant that has been implicated in the recruitment of eosinophils in allergic disease. We have investigated whether the cytokines interleukin (IL)-4, IL-13, and interferon (IFN)-gamma regulate eotaxin-2/CCL24 in nasal polyps. METHODS: Nasal polyps were cultured in the presence of the cytokines described above and the concentration of eotaxin-2/CCL24 was measured in the culture supernatant. RESULTS: IL-4 was found to be the major stimulus for eotaxin-2/CCL24 production from nasal polyps followed by IL-13 and IFN-gamma. IL-4 induced eotaxin-2/CCL24 in a dose-dependent manner with concentrations as low as 0.1 ng/ml being able to induce eotaxin-2/CCL24. By immunohistochemistry, eotaxin-2/CCL24 immunoreactivity was localized to mononuclear cells in the IL-4 stimulated nasal polyp tissue. Interestingly, nasal turbinates obtained from patients suffering from nonallergic rhinitis (vasomotor rhinitis) were also found to release eotaxin-2/CCL24 both spontaneously and following cytokine stimulation with IL-4 and IFN-gamma being major inducers of this cytokine. CONCLUSIONS: All together these findings suggest that Th1 and Th2 cytokines may regulate eotaxin-2/CCL24 production in nasal polyps and nonallergic rhinits.