白细胞介素-23在结核性脑膜炎早期诊断中的应用价值

目的检测早期结核性脑膜炎患者脑脊液中白细胞介素-23(IL-23)水平,探讨其在结核性脑膜炎发病机制中可能的作用及其临床意义。方法应用双抗体夹心酶联免疫吸附测定法,检测40例早期结核性脑膜炎治疗前以及治疗后以及37例病毒性脑膜炎患者脑脊液中IL-23的水平。结果与病毒性脑膜炎患者相比,结核性脑膜炎患者脑脊液中IL-23水平明显升高(P<0.01),而结核性脑膜炎患者脑脊液中IL-23水平在治疗1周后即明显下降(P<0.01),但仍较病毒性脑膜炎患者水平高(P<0.05)。结论 IL-23水平检测对了解结核病的活动性、判断病情及预后、监测疗效有一定的参考作用。     

CTD-ILD患者血清中SP-D、抗MDA5抗体、IL-6及TNF-α的变化及临床意义

目的探讨弥漫性结缔组织病变(CTD)合并肺间质病变(ILD)患者血清中肺表面活性蛋白D(SPD)、抗黑色素瘤分化相关基因抗体(MDA5)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平的变化及临床意义。方法选择2016年5月至2018年4月该院确诊的184例CTD患者,其中59例患者合并ILD。观察患者的临床表现,并进行肺部高分辨CT(HRCT)检查和肺功能检查。采用酶联免疫吸附检测法(ELISA)测定并比较所有受试者血清中SP-D、抗MDA5抗体、IL-6及TNF-α的水平。结果 CTD-ILD组患者血清中SP-D、抗MDA5抗体、IL-6水平均高于CTD患者,差异有统计学意义(P0.05)。经多因素logistic回归分析,CTD患者血清SP-D、抗MDA5抗体、IL-6水平升高是发生ILD的独立危险因素(P0.05)。对于CTD-ILD患者,无气短表现患者血清中SP-D水平低于出现气短表现的患者,无皮疹患者血清中抗MDA5抗体水平低于皮疹患者,差异有统计学意义(P0.05)。患者不同程度的肺通气障碍、弥散功能障碍及HRCT检查结果与患者血清中SP-D、抗MDA5抗体、IL-6及TNF-α的表达水平也密切相关(P0.05)。结论 SP-D和抗MDA5抗体可作为CTD患者发生ILD早期检测指标,而IL-6可作为肺纤维化检测指标,对于判断和预测CTD-ILD病情具有重要的临床指导意义。     

氨茶碱和醋酸强的松龙对哮喘病人单个核细胞分泌白介素的影响

目的:研究氨茶碱和类固醇激素对哮喘病人单个核细胞分泌白介素的影响。方法:本实验采用酶联免疫吸附检测法观察了正常人和哮喘病人外周血单个核细胞分别在脂多糖、氨茶碱、抗 IL-10抗体、醋酸强的松龙刺激24、48小时后培养液中 IL-5、IL-10的浓度变化。结果:经脂多糖刺激24、48小时后哮喘组 IL-5的浓度高于正常组,而 IL-10的浓度低于正常组(P<0.01);在24、48小时刺激时间后,哮喘病人氨茶碱-(10)组和氨茶碱-(20)组中 IL-5浓度均降低。(n=15,P<0.05),IL-10浓度均升高(n=15,P<0.05),在抗 IL-10抗体刺激24小时后,抗体组中 IL-5的浓度有升高的趋势,但差异无显著性(P>0.05,n=15);48小时后,抗体组中的 IL-5的浓度均明显高于氨茶碱组和对照组,差异有显著性(P<0.05,n=15)。醋酸强的松龙组在24、48小时刺激时间后 IL-5的浓度分别为:40.13±18.61pg/ml、低于检测敏感度,而 IL-10的浓度均低于检测敏感度。结论:内源性抑炎机制障碍(如:IL-10的分泌不足等)可能是哮喘发病的一个重要原因;氨茶碱具有通过促进外周血单个核细胞 IL-10生成而抑制 IL-5分泌的抗炎活性;类固醇激素的抗炎作用可能主要是通过抑制促炎因子(如:IL-5的生成等)而实现的,与 IL-10无关。     

中药强体种子方对脾肾两虚夹瘀型抗精子抗体阳性不孕症患者细胞因子水平的影响

目的:探讨中药强体种子方对脾肾两虚夹瘀型抗精子抗体阳性不孕症患者细胞因子水平的影响.方法:将血清抗精子抗体(AsAb)阳性患者随机分为两组,其中中药组23例,并设西药组22例对比,观察治疗后AsAb的下降率及细胞因子IL-1、IL-6、TNF-α的变化,AsAb、IL-1、IL-6、TNF-α应用酶联免疫吸附法(ELISA)测定.结果:中药组AsAb的转阴率及下降率明显高于西药组(P<0.05).两组患者治疗前血清IL-1、IL-6、TNF-α含量比较差异无显著性,治疗后显著下降,与治疗前比较差异有显著性(P<0.05),治疗后中药组与西药组比较.血清IL-1、IL-6、TNF-α含量明显下降,与治疗前比较差异有显著性(P<0.05).结论:中药强体种子方治疗脾肾两虚夹瘀型AsAb阳性不孕症抗体转阴及下降率快,治疗后IL-1、IL-6、TNF-α的水平明显下降,说明AsAb是不孕症的重要免疫因素,不孕患者血清中存在高水平的IL-1、IL-6、TNF-α.提示排卵期抗精子抗体阳性不孕患者体内的细胞免疫功能处于异常增强状态,中药强体种子方对AsAb所致的免疫性不孕有显著疗效,其治疗的可能机制在于下调了机体细胞因子的水平.     

充血性心力衰竭患者血清抗碳酸酐酶Ⅱ和Ⅲ自身抗体检测的意义

目的使用已建立的方法检测充血性心力衰竭(CHF)患者血清中的抗碳酸酐酶Ⅱ和Ⅲ自身抗体、抗氧化物及细胞因子水平,初步评价其临床意义。方法选取58例3个月~1年前曾发生心肌梗死的CHF患者和58名健康对照者,测定其血清抗碳酸酐酶Ⅱ和Ⅲ自身抗体、红细胞沉降率(ESR)、超氧化物歧化酶(SOD)等5种抗氧化物和白细胞介素2(IL-2)等5种细胞因子的水平。结果 CHF患者血清抗碳酸酐酶Ⅱ自身抗体和ESR水平显著高于对照组(P0.05),SOD、谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)和总抗氧化能力(TAC)显著低于对照组(P0.05),丙二醛(MDA)水平显著高于对照组(P0.05)。CHF患者血清的IL-2和白细胞介素17(IL-17)水平较对照组显著升高(P0.05),白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和γ干扰素(IFN-γ)与对照组差异无统计学意义(P0.05)。结论 CHF患者可能存在自身免疫的现象,IL-2、IL-17和抗氧化能力的检测可能作为判断抗碳酸酐酶Ⅱ抗体出现的指标。     

输血前后CD3/28双抗体活化外周血单个核细胞后细胞因子的变化

目的 研究单独CD3抗体或联合CD28抗体作用于输血前后患者外周血单个核细胞（PBMC）后细胞因子的变化。方法 体外T细胞培养与活化，采用酶联免疫法测定细胞因子IL-2、γ干扰索（IFN-γ）和IL-4的分泌水平。结果 输血前患者PBMC单独应用CD3抗体与联用CD28抗体后。PBMC细胞因子分泌水平的变化元显著性，但输血后差异有显著性。结论 CD28抗体可明显增强输血后体外活化T细胞功能，输血导致的免疫抑制作用可能与抗原提呈细胞的功能受到影响有关。     

乙型肝炎患者血清IL-16含量与其抗原抗体模式及HBV-DNA载量的关系研究

目的探索乙型肝炎患者抗原抗体模式、HBV-DNA载量与血清白细胞介素-16(IL-16)含量的相关性,为乙型肝炎发病机制的研究提供新的思路。方法用时间分辨荧光分析法(TRFIR)检测乙型肝炎血清标志物(HBsAg、抗-HBs、HBeAg、抗-HBe及抗-HBc IgG);用实时荧光定量聚合酶链反应(FQ-PCR)法检测HBV-DNA;用酶联免疫吸附法(ELISA)测定IL-16。结果乙型肝炎患者血清中IL-16含量与健康对照相比明显升高(P<0.01),并且1、3模式及1、3、5模式的患者血清中IL-16含量与1、4、5模式相比明显升高(P<0.01);HBV-DNA载量大于或等于500与HBV-DNA载量小于500的乙型肝炎患者血清IL-16水平相比明显升高(P<0.01)。结论血清IL-16在HBV感染早期病毒复制期明显升高,提示IL-16可能参与HBV感染后急性期的肝损伤过程,是一种潜在的乙型肝炎早期促炎性反应细胞因子。     

老年慢性支气管炎支气管哮喘患者IL-5及IL-8的变化

[目的]探讨IL-5,IL-8在老年慢性支气管哮喘,慢性支气管炎中的作用。[方法]应用双抗体夹心酶联免疫吸附法检测血清中IL-5及IL-8水平;借助纤维支气管镜,对11例支气管哮喘患者和9例慢性支气管炎患者行了支气管粘膜活检。通过原位杂交技术检测IL-5 mRNA及IL-8 mRNA的表达。[结果]支气管哮喘患者支气管粘膜有较高的IL-5 mRNA的表达：5例特应性哮喘患者IL-5 mRNA的杂交信号全部阳性,IL-8 mRNA的信号全部阴性;而在6例非特应性哮喘患者IL-5 mRNA的表达信号中,5例阳性,1例阴性,IL-8 mRNA的表达信号2例阳性,4例阴性．慢性支气管炎患者支气管粘膜则为IL-8 mRNA表达升高：5例慢性单纯型支气管炎患者IL-5 mRNA表达皆阴性,IL-8 mRNA的表达皆阳性;4例慢性喘息型支气管炎患者IL-5 mRNA的表达为1例阴性,3例阳性;IL-8 mRNA的表达则全部阳性。[结论]IL-5和IL-8参与了慢性支气管炎的发病。     

人白细胞介素-29 cDNA克隆及其在大肠杆菌系统的表达

目的：克隆人细胞因子IL-29全长cDNA及其在大肠杆菌中表达,制备抗IL-29多克隆抗体。方法：分离外周血单核细胞;VSV感染后,提取总RNA,通过一步RT-PCR获得IL-29全长cDNA。DNA测序正确后,将IL-29cDNA的编码框序列构建到原核表达载体pET28a(+)中。卡那霉素平板筛选及PCR鉴定,挑出阳性克隆进行扩增、转化大肠杆茵进行IPTG诱导表达。SDS-PAGE、Western blotting鉴定,亲和层析分离纯化得到Mr为23000组氨酸标签重组人IL-29融合蛋白。纯化的IL-29免疫家兔制备抗IL-29多克隆抗体。结果：成功获得人IL-29全长cDNA,并以包涵体形式表达于大肠杆茵中。免疫家兔后获得特异抗IL-29的多克隆抗体。结论：获得rhlL-29细胞因子及其多克隆抗体,为其进一步研究及应用奠定基础。     

免疫不孕症患者外周血Th1、Th2细胞因子与血清AhCGAb、AsAb、AoAb相关抗体的关系

目的探讨免疫不孕症患者外周血特异性T辅助细胞(Th)1、Th2细胞因子与血清抗人绒毛膜促性腺激素抗体(AhCGAb)、抗精子抗体(AsAb)、抗卵巢抗体(AoAb)相关抗体的关系。方法选取2014年2月至2015年12月在该院就诊的58例免疫不孕症患者作为试验组,同时期选取60例孕育功能正常的健康妇女为对照组。应用酶联免疫吸附测定(ELISA)检测两组受试对象的Th细胞因子水平(IL-2、IL-21、IFN-γ、TNF-α、IL-4、IL-6、IL-10)及AhCGAb、AsAb、AoAb的表达,并分析其相关性。结果与对照组相比,试验组Th1型细胞因子IL-2、IL-21、IFN-γ、TNF-α水平明显高于对照组,差异有统计学意义(P0.05);Th2型细胞因子IL-4、IL-6、IL-10水平也高于对照组,但仅有IL-4和IL-6指标差异有统计学意义(P0.05)。抗体结果显示,试验组各相关抗体阳性率明显高于对照组,差异有统计学意义(P0.05)。相关性分析显示,IL-21与AhCGAb、AsAb、AoAb的产生呈正相关(r=0.612、0.603、0.726,P0.05);IL-6与AhCGAb、AsAb、AoAb的产生呈正相关(r=0.426、0.479、0.616,P0.05)。TNF-α与AoAb的产生呈负相关(r=-0.544,P0.05)。结论免疫不孕症患者外周血Th1、Th2细胞因子与血清AhCGAb、AsAb、AoAb相关抗体有一定相关性;AhCGAb、AsAb、AoAb 3种抗体的检测和定量作为免疫不孕症的诊断指标具有一定临床意义。     

Eosinophilic bronchitis: an imortant cause of prolonged cough

The recent development of noninvasive techniques to measure airway inflammation has led to the recognition of eosinophilic bronchitis, a condition characterized by a sputum eosinophilia identical to that seen in asthma, but without any of the functional abnormalities associated with asthma. The condition is interesting for a number of reasons. Firstly, eosinophilic bronchitis is a common cause of chronic cough, which is important to recognize as it responds well to corticosteroids. However, recognition is not straightforward because it requires assessment of airway inflammation. Secondly, the natural history of eosinophilic bronchitis is uncertain. Some patients with chronic obstructive pulmonary disease without a history of previous asthma have sputum eosinophilia, thus one possibility is that eosinophilic bronchitis may develop into fixed airflow obstruction. Finally, the difference in the association of eosinophilic airway inflammation to airway dysfunction between eosinophilic bronchitis and asthma is of interest as it is possible that it reflects important differences in the nature or site of the airway inflammation. Further study of this interesting condition may shed light on the relationship between airway inflammation and airway responsiveness, leading to a greater understanding of both eosinophilic bronchitis and asthma.     

Eosinophilic bronchitis: an important cause of prolonged cough

The recent development of noninvasive techniques to measure airway inflammation has led to the recognition of eosinophilic bronchitis, a condition characterized by a sputum eosinophilia identical to that seen in asthma, but without any of the functional abnormalities associated with asthma. The condition is interesting for a number of reasons. Firstly, eosinophilic bronchitis is a common cause of chronic cough, which is important to recognize as it responds well to corticosteroids. However, recognition is not straightforward because it requires assessment of airway inflammation. Secondly, the natural history of eosinophilic bronchitis is uncertain. Some patients with chronic obstructive pulmonary disease without a history of previous asthma have sputum eosinophilia, thus one possibility is that eosinophilic bronchitis may develop into fixed airflow obstruction. Finally, the difference in the association of eosinophilic airway inflammation to airway dysfunction between eosinophilic bronchitis and asthma is of interest as it is possible that it reflects important differences in the nature or site of the airway inflammation. Further study of this interesting condition may shed light on the relationship between airway inflammation and airway responsiveness, leading to a greater understanding of both eosinophilic bronchitis and asthma.     

May mepolizumab used in asthma correct subfertility?

İntroductionAsthma is one of the most common chronic airway disease among reproductive period of women. Chronic inflammation in asthma, eosinophilia, high steroid treatment and uncontrolled asthma may cause infertility by affecting the reproductive organs, menstrual cycle and quality of life. Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids. Mepolizumab (anti-IL-5) is a succesful option of treatment.CasesFirst case; 25-year-old female patient has been diagnosed having asthma and rhinitis for 5 years. Even she had desired pregnancy for 3 years, she was unable to have a baby, and had been diagnosed having primary infertility. Second case; 36 years old female had rhinitis for 6 years and asthma for 4 years Although she used the same contraception method (withdrawal,condom) for years, she did not get pregnant until receiving the second dose of mepolizumab treatment.ResultTwo women were treated with mepolizumab for eosinophilic severe asthma and they got pregnant.ConclusionUnexplained infertility in people with severe eosinophilic asthma may be corrected by mepolizumab treatment. However, there is not enough data regarding the use of mepolizumab during pregnancy.     

Targeting of eosinophils in asthma

Severe asthma continues to be an important source of morbidity despite the availability of bronchodilators and corticosteroids. Although new treatments are needed, better identification of asthma phenotypes may improve treatment effectiveness. One phenotype that has emerged is eosinophilic asthma. Eosinophils in asthma have been studied for many years, and the evidence suggests they play a major role in some forms of asthma. Eosinophilic asthma can be diagnosed using peripheral blood, sputum eosinophil count or exhaled nitric oxide. Depletion of eosinophils can be achieved by corticosteroids, specific anti-interleukin 5 (IL-5) or anti-IL-5-receptor-alpha therapies, or anti-immunoglobulin E approaches. This editorial refers to the approaches that are being taken in eosinophilic asthma with emphasis on the new investigational anti-IL-5-receptor-alpha antibody, benralizumab.     

Targeting of eosinophils in asthma

Severe asthma continues to be an important source of morbidity despite the availability of bronchodilators and corticosteroids. Although new treatments are needed, better identification of asthma phenotypes may improve treatment effectiveness. One phenotype that has emerged is eosinophilic asthma. Eosinophils in asthma have been studied for many years, and the evidence suggests they play a major role in some forms of asthma. Eosinophilic asthma can be diagnosed using peripheral blood, sputum eosinophil count or exhaled nitric oxide. Depletion of eosinophils can be achieved by corticosteroids, specific anti-interleukin 5 (IL-5) or anti-IL-5-receptor-alpha therapies, or anti-immunoglobulin E approaches. This editorial refers to the approaches that are being taken in eosinophilic asthma with emphasis on the new investigational anti-IL-5-receptor-alpha antibody, benralizumab.     

Immunological basis of reversible and fixed airways disease

Asthma is characterized by airflow obstruction that is usually completely reversible either spontaneously or in response to treatment. However, a small subset of patients with asthma display FAO (fixed airflow obstruction) despite optimal treatment, a feature more commonly associated with smoking-induced COPD (chronic obstructive pulmonary disease). Why some asthma patients develop FAO is not understood, and it is not clear whether (i) they represent a subset of patients with more severe disease, (ii) they share some characteristics of patients who develop COPD, or (iii) they represent a different disease entity altogether. The present review compares the pulmonary inflammatory profile of asthma patients with FAO with those without FAO, as well as COPD sufferers. The inflammation in asthma patients with FAO can vary from neutrophilic with CD8 T-cell involvement, similar to that of COPD, to eosinophilic with CD4 Th2 cell involvement, akin to that of asthma patients without FAO. Although studies of FAO in asthma sufferers would benefit hugely from consistent inclusion criteria, further research work is also required to shed more light on the immunological processes involved.     

Treatment of severe asthma: entering the era of targeted therapy

Introduction: It is estimated that 5 – 10% of asthma patients suffer from severe asthma. Severe asthma is associated with increased morbidity and mortality. These patients are not controlled with currently available treatments and therefore additional treatment options are needed. Asthma is a heterogeneous disease, and different asthma patient groups probably have different underlying pathophysiology. Novel therapies with, for example, monoclonal antibodies that target certain immunological pathways have become available. These novel treatments are not effective in all patients but only in certain phenotypes.

Areas covered: This review covers the current evidence and novel developments in treatment with monoclonal antibodies in different asthma phenotypes. This includes monoclonal antibodies against IgE, against interleukin (IL)-5 and antibodies targeting IL-13 pathways. Although there is a certain overlap between patient groups benefiting from these treatments, a more detailed identification of responder profiles for these therapies is needed for personalized therapy.

Expert opinion: In recent years, novel monoclonal antibodies have been developed, which are a promising addition to existing therapy in the treatment of severe asthma with eosinophilic inflammation and Th2-driven disease. We expect that several of the new antibodies will become available for clinical practice. In addition, it must be acknowledged that so far no effective strategies are available for patients with non-eosinophilic asthma and further research and development is necessary for this patient group.     

Eosinophilic airway diseases presenting with isolated cough except for asthma]

Cough variant asthma (CVA), atopic cough (AC) and eosinophilic bronchitis without asthma (EB) are eosinophilic airway diseases presenting with isolated chronic cough. Among them, bronchodilators are effective only in CVA. Bronchial responsiveness, diurnal variation of pulmonary function and bronchomotor tone are mildly increased to intermediate levels between mild asthma and normal in CVA, but not in AC or EB. Cough sensitivity is heightened in atopic cough and probably in EB, but not in CVA. Bronchoalveolar lavage eosinophilia is present in CVA and EB, but absent in AC. As asthma onset has been recognized in nearly 30% patients with CVA, but not in AC, long-term inhaled corticosteroid therapy is recommended only in CVA.     

肺炎衣原体感染与哮喘关系的探讨

目的探讨肺炎衣原体(Chlamydiapneumoniae,CP)感染与哮喘发病的可能关系。方法应用免疫荧光法检测86例近期哮喘患者血清中CP特异性IgG抗体,同时作全血嗜酸性粒细胞计数。以健康体检者作为对照。结果近期哮喘患者CP特异性IgG抗体滴度显著高于正常对照组(P<0.05),且与嗜酸性粒细胞计数呈正相关(r=0.631,P<0.05),有统计学意义。抗体滴度阳性率、CP急性感染率与慢性感染率,均显著高于正常对照组(P<0.05)。结论CP感染与哮喘的发病密切相关。     

New insights into the relationship between airway inflammation and asthma

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.