支气管哮喘患者血清IL-6、TNF-α、IgE检测的临床分析

目的：探讨对支气管哮喘患者进行白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、IgE检测的临床意义。方法：通过观察36例急性支气管哮喘发作期患者（哮喘组）治疗前后血清IL-6、TNF-α、IgE含量的动态变化,并与健康体检者（对照组）比较。结果：哮喘组哮喘发作期患者血清IL-6、TNF-α、IgE含量均明显高于对照组（均P〈0.01）;哮喘缓解后即刻IL-6、TNF-α、IgE含量均较哮喘发作期有明显下降（均P〈0.01）;哮喘缓解后14d,IL-6、TNF-α、IgE含量较哮喘缓解后即刻又有明显下降（均P〈0.01）,但仍较对照组高（均P〈0.05）。IL-6、TNF-α含量和IgE含量均呈正相关（r=0.618,P〈0.01;r=0.723,P〈0.01）。结论：支气管哮喘病情的严重程度与IL-6、TNF-α、IgE含量密切相关,临床可以通过检测IL-6、TNF-α、IgE的含量作为判断支气管哮喘病情严重程度和治疗效果的重要指标。     

儿童过敏性哮喘患者外周血白细胞介素17的变化

目的 研究儿童过敏性哮喘患者外周血白细胞介素(IL) 17 mRNA和蛋白水平的变化.方法 广州中医药大学第一附属医院收治的30例过敏性哮喘发作期患儿,25例哮喘缓解期患儿和30例健康儿童,采用实时荧光定量PCR相对定量法检测儿童的外周血IL-17 mRNA水平的变化,采用ELISA法检测各组血浆中IL-17蛋白水平的变化.结果 哮喘发作期患儿IL-17 mRNA表达显著升高,明显高于缓解期患儿和健康儿童[(10.20±3.32)％比(8.61±1.62)％和(3.84±1.36)％,均P＜0.05];哮喘发作期患儿IL-17蛋白表达明显高于缓解期患儿和健康儿童(P＜0.05).结论 过敏性哮喘发作期患儿外周血出现IL-17表达明显上升,提示IL-17在过敏性哮喘发病过程中起着重要作用.     

细胞因子信号抑制因子在支气管哮喘TH1/TH2细胞失衡中的作用

目的 探讨细胞因子信号抑制因子（SOCS）在支气管哮喘（简称哮喘）患儿TH细胞亚群（TH1／TH2）功能失衡中的作用，以及转录因子T-bet和GATA3与TH1／TH2反应的关系。方法 观察20例哮喘患儿及相同数量同龄对照，采用流式细胞术（FCM）检测哮喘患者外周血CD4^＋T淋巴细胞浆中白细胞介素4（IL-4）和γ干扰素（INF-γ）的表达，逆转录-聚合酶链反应（RT-PCR）和荧光定量聚合酶链反应（real time PCR）测定淋巴细胞SOCS3、SOCS5、T-bet、GATA3 mRNA表达水平。结果 急性发作期哮喘患儿TH1细胞比例显著下降，TH2细胞显著增高（P〈0．01）；哮喘患儿淋巴细胞SOCS3、GATA3 mRNA表达水平显著高于正常同龄对照（P〈0．01），SOCS5、T-bet mRNA表达显著下降（P〈0．01）。结论 SOCS3、SOCS5、T-bet和GATA3表达异常与哮喘患儿TH1／TH2失衡有关，其中SOCS3和SOCS5表达异常可能是重要的因素之一。     

IL-6、IL-8、TNF-α及IFN-α在儿童哮喘不同病期的变化

检测哮喘发作期（35例）、稳定期（18例）及正常对照组（28例）血清IL-6、IL-8、TNF-α和IFN-α水平。结果表明哮喘发作期IL-6、IL-8、TNF-α水平明显增高,而IFN-α显著降低;至稳定期血清IL-6、IL-8、TNF-α恢复到对照组水平,唯IFN-α仍低于正常儿。血清THN-α与IL-6、IL-8、IFN-α间存在正相关关系。提示哮喘患儿存在多种细胞因子产生和释放异常。细胞因子网络失调可能是哮喘发病的分子生物学基础。     

支气管哮喘患者B淋巴细胞膜CD23的变化及临床意义

支气管哮喘是一种气道慢性炎症性疾病，其发病机制之一是在致病原的作用下，Th1／Tb2失衡，其分泌的细胞因子激活B淋巴细胞，合成和分泌大量的IgE。而CD23为IgE低亲合力受体，是B淋巴细胞激活的表面标志。故研究哮喘患者CD23的表达具有意义。本研究以CD19作为总B淋巴细胞标志分别对正常人和哮喘患者发作期及缓解期外周     

支气管哮喘患者血清TNF-α、IL-8和IgE水平的相关性分析

目的 探讨支气管哮喘患者血清TNF-α、IL-8和IgE的关系及意义.方法 采用酶联法对33例支气管哮喘患者进行了血清TNF-α、IL-8和IgE检测,并与35名正常人作比较.结果 支气管哮喘患者血清TNF-α、IL-8和IgE水平均非常显著地高于正常人组（P〈0.01）,经治疗1个月后与正常人组比较仍有显著性差异（P〈0.05）,血清IgE水平与TNF-α、IL-8水平呈显著正相关（r=0.5712、0.6018,P〈0.01）.结论 检测血清TNF-α、IL-8和IgE含量可作为判断支气管哮喘病情的严重程度和治疗效果的重要指标.     

血浆sIL-2R对急性期川崎病调节性T 细胞的影响

目的探讨sIL-2R血浓度对急性期川崎病（ KD）患儿调节性T细胞（ Treg）的影响。方法急性期KD患儿33例,正常同龄对照儿童14例。流式细胞术检测外周血CD4＋CD25＋Foxp3＋Treg细胞的比例和CD4＋CD25＋T细胞磷酸化STAT5（pSTAT5）蛋白平均荧光强度（MFI）;流式微球阵列术（CBA）检测血浆sIL-2R、IL-2、IL-7、IL-15的浓度;荧光定量PCR（real-time PCR）检测CD4＋CD25＋T细胞Foxp3、GITR、CTLA-4、IL-2Rα、IL-2Rβ、IL-2Rγ和CD 4＋CD25-T 细胞 IL-17A、RoR-γt 等基因mRNA表达。结果（1）急性期KD患儿CD4＋CD25＋Foxp3＋Treg细胞比例及相关分子Foxp3、GITR、CTLA-4 mRNA表达明显低于同龄对照组（P＜0．05）,Th17细胞相关因子IL-17A、ROR-γt mRNA表达明显增高（P＜0．05）,IVIG治疗后呈不同程度的恢复（P＜0．05）。（2）急性期KD患儿CD4＋CD25＋T细胞pSTAT5蛋白水平显著下调（P＜0．05）,IVIG治疗后明显上调（P＜0．05）。（3）急性期KD患儿血浆sIL-2R浓度显著增高（P＜0．05）,IVIG治疗后下降（P＜0．05）;其中KD合并冠脉损伤组（KD-CAL＋）明显高于无冠脉损伤组（KD-CAL-）（P＜0．05）;IL-2、IL-7、IL1-5浓度无明显改变（P＞0．05）。（4）急性期KD患儿CD4＋CD25＋T细胞IL-2Rα、IL-2Rβ基因mRNA表达明显低于同龄对照组（P＜0．05）,IVIG治疗后呈不同程度的升高（ P＜0．05）;IL-2Rγ基因mRNA表达无明显改变;sIL-2R血浓度与IL-2RβmRNA、pSTAT5及Foxp3 mRNA表达呈负相关（ P＜0．05）;pSTAT5与Foxp3 mRNA表达呈正相关（ P＜0．05）。结论血浆sIL-2R明显增高可致IL-2/STAT5信号途径传导异常,这可能是导致急性期KD Treg细胞下调的因素之一。     

IL-31在哮喘小鼠中的动态表达及对肺泡上皮细胞表达CCL11和CCL22的影响

目的通过观察IL-31在OVA诱导小鼠哮喘模型中的动态表达及IL-31对肺泡上皮细胞表达趋化因子CCL11和CCL22的影响,探讨IL-31在哮喘气道炎症中的作用。方法常规OVA法建立小鼠哮喘模型,于末次激发后取肺组织HE染色及AB-PAS染色,收集支气管肺泡灌洗液(BALF)进行白细胞和嗜酸性粒细胞(EOS)计数,ELISA法检测血浆中IgE、IL-4、IFN-γ、IL-31水平,荧光定量PCR检测肺组织IL-31R mRNA表达水平,同时体外培养小鼠肺泡上皮细胞,用IL-31处理24 h后检测CCL11和CCL22 mRNA的表达水平。结果成功构建哮喘小鼠模型,哮喘小鼠BALF中白细胞总数、嗜酸性粒细胞百分比和血浆中IgE水平明显增多。哮喘小鼠肺组织病理切片见中性粒细胞、EOS浸润。哮喘小鼠血浆中Th2类细胞因子IL-4水平明显高于对照组,Th1类细胞因子IFN-γ明显低于对照组。哮喘小鼠血浆IL-31水平和肺组织IL-31R mRNA表达水平明显增高,第2周至第8周虽略有降低但仍明显高于对照组。IL-31作用小鼠肺泡上皮细胞24h后,趋化因子CCL11、CCL22mRNA表达增高。结论IL-31通过刺激趋化因子表达募集炎性细胞,促进气道炎症的发生发展。     

血清骨膜蛋白和脂联素联检诊断儿童支气管哮喘价值研究

目的 探讨支气管哮喘患儿血清骨膜蛋白及脂联素（ADP）水平检测对诊断支气管哮喘的临床价值。方法 选取选取2017年1月~12月在常州儿童医院儿科就诊的40例支气管哮喘患儿（哮喘组）和40名同期健康儿童体检者（对照组）作为研究对象,ELISA法检测哮喘组急性发作期和缓解期及对照组的血清Periostin、ADP及IgE水平;采用ROC曲线评价Periostin及ADP对支气管哮喘病情评估效能预测。结果 哮喘组患儿发作期及缓解期血清Periostin和血清ADP水平均高于对照组（P＜0.05）且发作期高于缓解期（P＜0.05）;采用血清Periostin和ADP水平诊断支气管哮喘,其诊断灵敏度分别为85.02%和80.48%,特异度为92.51%和81.98%,当血清Periostin和血清ADP分别在147.52 μg/L和20.31 mg/L时,其Youden 值最大,分别为0.7752和0.7504,其AUC分别为0.8262和0.7823,两者联检可将灵敏度和特异性分别提高到87.03%和95.52%。支气管哮喘急性发作期和缓解期血清Periostin与IgE的相关系数分别为0.9916和0.9358,而急性发作期和缓解期血清ADP与IgE的相关系数分别为0.4767和0.2344。结论　动态监测支气管哮喘患儿血清中Periostin及ADP水平有助于判断支气管哮喘病情转归效果;二者联检可作为排查儿童支气管哮喘的指标,血清Periostin可作为诊断支气管哮喘良好血清学指标。     

孟鲁司特对支气管哮喘患者体内炎症水平的影响

目的：研究孟鲁司特对支气管哮喘患者外周血嗜酸性粒细胞（EOS）、NF-kB、TNF-α、IL-10的影响。方法：检测40例急性发作期哮喘患者（哮喘组）孟鲁司特治疗前后外周血EOS、NF-kB活性、TNF-α、IL-10的水平变化,并与40例健康体检人员（对照组）作比较。结果：哮喘患者（治疗前）外周血EOS、NF-kB、TNF-α水平都明显高于对照组（P〈0.05）,IL-10水平明显低于对照组（P〈0.05）。哮喘患者治疗后,外周血EOS、NF-kB、TNF-α水平明显下降（P〈0.05）,IL-10水平明显升高（P〈0.05）。结论：孟鲁司特对哮喘患者外周血EOS、NF-kB、TNF-α、IL-10的水平有一定程度的调节作用,从而降低支气管哮喘患者体内炎症水平,促进病情缓解与好转。     

哮喘患儿血浆NO、IL和TNF的变化及意义

采用镉还原柱层析和比色法测定了42例哮喘患儿外周血亚硝酸/硝酸根离子(NO_2~-/NO_3~-)水平,另用生物学活性法测定了白细胞介素2、4、6(IL-2、4、6)及肿瘤坏死因子(TNF)水平.结果:小儿哮喘发作期外周血IL-2、4、6,TNF及NO水平均明显高于正常儿童(P分别<0.05,<0.01);在缓解期IL-2,6,NO水平恢复正常水平(P均>0.05),而IL-4,TNF水平虽较发作期有明显降低,但仍高于正常儿童(P均<0.01).提示:NO,IL-2、4、6及TNF参与了哮喘的病理生理过程,是哮喘气道高反应性及变应性炎症的重要介质,在哮喘的免疫发病机制中占有重要地位.     

外周血T细胞亚群及细胞因子对外源性哮喘IgE生成的作用

对３０例哮喘患者及３０例健康成年人的外周血，采用单克隆抗体（ＭｃＡｂ）间接免疫荧光法测定Ｔ细胞亚群；ＥＬＩＳＡ双抗体夹心法测定ＩｇＥ、ＩＬ－４；ＦＩ２细胞株，生物学方法测定ＩＬ－２；ＩＬ－６依赖细胞株７ＴＤ１，掺入法测定ＩＬ－６；用抗人ＣＤ２３的ＭｃＡｂ测定ＣＤ２３。为研究Ｔ细胞、细胞因子对哮喘ＩｇＥ生成调节机理及细胞因子在哮喘发病过程中的作用。结果显示：发作期ＩｇＥ、ＩＬ－２、ＩＬ－４、ＣＤ２３、ＣＤ８~＋、ＣＤ４／ＣＤ８~＋比值较对照组及缓解期有显著性差异（Ｐ＜０．０１）。缓解期ＩｇＥ与对照组之间无显著性差异（Ｐ＞０．０５）；ＣＤ８＋、ＣＤ４／ＣＤ８比值，ＣＤ２３与对照组之间有显著性差异（Ｐ＜０．０１）。ＣＤ２３、ＣＤ４、ＩＬ－６三组间无显著性差异（Ｐ＞０．０５）。结果表明，ＩｇＥ合成增加是哮喘发作的关键，Ｔ细胞对日细胞合成ＩｇＥ的调节是通过细胞因子实现的，细胞因子又参与气道炎症过程。     

Distribution and cytokine production of CD4 and CD8 T-lymphocyte subsets in patients with acute asthma attacks.

BACKGROUND: The activation of T cells and the elevation of Th2-type cytokines have been observed in asthmatic patients, but the relative role of CD4 and CD8 T cell is still unclear. OBJECTIVE: To investigate the role of T cell subset in patients with acute asthma attacks, we analyzed the distribution, activation status, and cytokine production of CD4 and CD8 cells. METHODS: The percentages of the CD4 and CD8 cell in peripheral blood (PB) and bronchoalveolar lavage (BAL) fluid were analyzed by flow cytometry. The cytokines (IL-4, IL-5, and IFN-gamma) and soluble IL-2 receptor (sIL-2R) were measured by ELISA in culture supernatants of CD4 and CD8 cells purified from PB. RESULTS: The CD4/CD8 ratio in PB of asthmatic patients was significantly higher than that of controls, which was significantly reduced after treatment. In contrast, there was a tendency to high percentage of CD8 cells in asthmatic patients as compared with controls in BAL, which resulted in a decreased CD4/CD8 ratio. Comparing the T cell subsets in BAL with paired PB in asthma, the CD4 cells were higher in PB, but CD8 cells were higher in BAL. The IL-4, IL-5, and sIL-2R produced by CD4 cells were significantly higher than those produced by CD8 cells in asthmatic patients. CONCLUSIONS: Our results provide evidence that activated CD4 T cells increase and produce type 2 cytokines in PB, but CD8 T cell are more sequestrated than CD4 T cells in the airway during an acute asthma attack.     

Specific immunoglobulin E for staphylococcal enterotoxins in nasal polyps from patients with aspirin-intolerant asthma

BACKGROUND: Nasal polyps infiltrated with eosinophils are commonly found in chronic asthmatic patients, more frequently in those with aspirin-intolerant asthma (AIA) than aspirin-tolerant asthma (ATA). Some studies have suggested a contribution of superantigens derived from Staphylococcus sp to nasal polyposis and eosinophilia, but their relative importance in AIA and ATA subjects is unknown. OBJECTIVE: We investigated whether local production of specific IgE to staphylococcal enterotoxins A and B (SEA and SEB) and relationships with markers of eosinophilic inflammation differ in the nasal polyps of AIA and ATA subjects. METHODS: Fifteen AIA subjects with positive responses to lysine-aspirin bronchoprovocation and 15 ATA subjects underwent polypectomy. Immunoassays were used to quantify eosinophil cationic protein (ECP), IL-5, mast cell tryptase, soluble IL-2 receptors (sIL-2R), total IgE, and specific IgE for SEA and SEB. RESULTS: ECP levels in nasal polyp homogenates were higher in AIA subjects than in ATA subjects (P < 0.02), with no significant differences in tryptase, IL-5 or sIL-2R. Total IgE, and specific IgE to both SEA and SEB, were detectable in some nasal polyps from both subject groups, but median levels were markedly higher in AIA subjects than in ATA subjects (P = 0.04, 0.01, 0.05, respectively). Levels of specific IgE to SEA and SEB correlated significantly with levels of ECP and IL-5, but not those of tryptase or sIL-2R. CONCLUSION: These findings suggest that staphylococcal superantigens may drive local eosinophilic inflammation in nasal polyp tissue, and that this is exacerbated in subjects with AIA.     

IL－2和sIL－2R在哮喘发病中的意义探讨

为了探讨ＩＬ－２和ｓＩＬ－２Ｒ在哮喘发病中的意义，对３６例哮喘患者外周血单个核细胞（ＰＢＭＣ）诱生ＩＬ－２水平和血浆ｓＩＬ－２Ｒ水平进行了检测，同时以支气管炎患者与正常人作对照。结果表明，ＰＢＭｃ诱生的ＩＬ－２活性哮喘组高于正常对照组（ｐ＜０．０５）；血浆ｓＩＬ－２Ｒ水平哮喘组高于支气管炎和正常组（ｐ＜０．０１），后两者差异无显著性。以上结果表明，哮喘发病中存在着Ｔ细胞的活化，ＩＬ－２／ＩＬ－２Ｒ在哮喘发病中起作用。     

Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children before and after a prednisolone course.

BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the disease activity of acute asthma, changes in serum concentrations of sIL-2R and IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined in the present study. METHODS: Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in a stable condition were determined by using commercially available ELISA kits. RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2 +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P < .001). The mean concentration of serum IL-4 was higher in acute exacerbation (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL) versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was not statistically significant among the three study groups. CONCLUSIONS: This study provides further evidence that changes in serum IL-2R may serve as an objective indicator for clinical outcome of allergic asthmatic patients.     

T cell and eosinophil activation in mild and moderate atopic and nonatopic children's asthma in remission

BACKGROUND: Inflammation in the pathogenesis of asthma is associated with products of activated T cells and eosinophils. The aim of this study was to determine whether ongoing inflammation persists in children with different phenotypes of asthma despite the disease in remission. METHODS: Serum samples were collected from 68 children with atopic or nonatopic asthma in remission and from 15 healthy children. Soluble interleukin-2 receptor (sIL-2R), IL-2 and IL-4 were examined by using an enzyme-linked immunosorbent assay. Total and specific immunoglobulin E, and eosinophil cationic protein (ECP) were analysed by fluoroimmunoassay (Pharmacia CAP System). RESULTS: In patients with moderate persistent atopic asthma, sIL-2R was increased significantly when compared with mild persistent atopic asthma (P < 0.05). No changes of sIL-2R were seen in nonatopic asthmatics compared with atopics and controls. The level of IL-2 was elevated in moderate persistent atopic and nonatopic asthmatic children compared with controls (P < 0.05 and P < 0.05 respectively) and compared with mild persistent atopic asthmatics and mild persistent nonatopic asthmatics (P < 0.05 in both cases). The levels of IL-4 in most patients and controls remained below the sensitivity of the assay. Eosinophil cationic protein levels in moderate persistent atopic and nonatopic asthmatics were significantly higher than in mild persistent asthma severity cases (P < 0.001 and P < 0.01 respectively) and in healthy children (P < 0.01 in both cases). CONCLUSION: Changes in the concentration of sIL-2R, IL-2 and ECP reflect increased T cell and eosinophil activity in relation to the level of severity of asthma in atopic and nonatopic children, thereby proving the presence of persistent inflammation despite the absence of disease symptoms.     

Serum levels of soluble IL-2 receptor, IL-4 and IgE-binding factors in childhood allergic diseases.

The serum levels of soluble IL-2 receptor (sIL-2R), IL-4 and IgE-binding factors were examined in children with allergic diseases, and compared with those in non-allergic controls of the same age and sex. The results showed age-related decreases in the serum levels of sIL-2R and IgE-binding factors, but not in that of IL-4 in both allergic and non-allergic individuals. Significant elevation of sIL-2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non-allergic controls. The serum concentration of IL-4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non-allergic controls, and was correlated significantly with the serum level of IgE (r = 0.59). The IgE-binding factor levels in sera from patients aged 6-10 years with bronchial asthma, or patients aged 1-5 years with a history of food anaphylaxis were elevated as compared with those in non-allergic controls of same age. There was no significant correlation between the serum levels of IgE-binding factors and IgE. Since sIL-2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL-4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL-4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE-binding factors in the age-related changes of clinical manifestations in childhood allergic diseases was also discussed.