TH1细胞在呼吸道合胞病毒毛细支气管炎发病机制中的作用

目的：探讨呼吸道合胞病毒（RSV）毛细支气管炎（毛支）发病中是否存在THl细胞免疫反应。方法：用ELISA法检测58例RSV毛支患儿急性期血浆IL-2含量。根据临床评分标准、供氧和住院时间长短的标准，进行严重程度分组并比较。结果：RSV毛支急性期血浆IL-2含量变化很大（0～4175ng／ml），中位数96ng／ml（4．0～530．1）。各组间比较，IL-2水平差异无显著性（均P〉0.05）；且IL-2水平与各严重因素无明显相关性（P〉0．05）。结论：TH1细胞可能不参与RSV毛支的发病机制，IL-2的改变可能系其他原因所致。     

毛细支气管炎患儿PBMCs产生IL-4和IFN-γ水平及意义

本文用ELISA法测定毛细支气管炎（毛支）急性期患儿20例和健康对照组15例外周血单个核细胞（PBMCs）培养上清中IL-4和IFN-γ水平。结果表明,毛支组PBMCs产生IL-4水平明显高于对照组,均数分别为102.46±48.22ng/L和50.41±21.36ng/L（P<0.01）;IFN-γ水平则明显低于对照组,均数分别为616.10±235.32ng/L和1468.1±503.60ng/L（P<0.01）。经直线相关分析,IL-4与IFN-γ呈明显负相关（P<0.01）。提示毛支患儿IL-4/IFN-γ产生失衡,可能与随后发生哮喘有关。     

孟鲁司特在小儿呼吸道合胞病毒毛细支气管炎治疗中的应用效果分析

目的 探讨孟鲁司特在小儿呼吸道合胞病毒毛细支气管炎治疗中的应用效果.方法 以2013年2月到2014年1月我院收治的86例呼吸道合胞病毒毛细支气管炎患儿为研究对象,随机分为两组,分别进行孟鲁司特治疗(治疗组)和常规综合性治疗(对照组).比较两组临床疗效、喘息缓解时间、住院时间、咳嗽、啰音、喘憋、鸣音等症状消失时间、半胱氨酰白三烯(CysLTs)、嗜酸性粒细胞阳离子蛋白(ECP)变化及复发情况.结果 治疗组总有效率为95.35％,对照组总有效率为74.42％.两组临床疗效比较,差异具有统计学意义(P＜0.05).治疗组喘息缓解时间、住院时间、症状消失时间均明显低于对照组,差异具有统计学意义(P＜0.05).治疗前,两组CysLTs、ECP无明显差异,不具有统计学意义(P＞0.05).治疗后,治疗组CysLTs、ECP均明显低于对照组(P＜0.05).治疗组复发3例(6.98％),对照组复发12例(27.91％),差异具有统计学意义(P＜0.05).结论 孟鲁司特治疗小儿RSV毛细支气管炎疗效确切、安全可靠,具有起效快、并发症少的特点,值得临床推广 .     

IFN－γ和IL－4对IgE生成的调节作用探讨

本文通过对鸡蛋过敏患者血清及外周血单个核细胞（ＰＢＭＣｓ）培养上清的ＩｇＥ水平测定，探讨了γ－干扰素（ＩＦＮ－γ）、白细胞介素４（ＩＬ－４）参与ＩｇＥ生成的调节机制。结果表明：ＩＦＮ－γ可抑制ＩｇＥ的生成，而ＩＬ－４则相反。ＰＢＭＣｓ培养上清中ＩＦＮ－γ和ＩＬ－４与ＩｇＥ浓度之间呈显著相关。     

孟鲁司特钠治疗呼吸道合胞病毒感染的毛细支气管炎效果与安全性

目的:探讨孟鲁司特钠治疗呼吸道合胞病毒感染的毛细支气管炎效果与安全性。方法:选取2018年1月至2019年1月在我院就诊的78例呼吸道合胞病毒感染的毛细支气管炎患儿,按照治疗方式的不同分为对照组和观察组(n=39)。对照组患儿每日雾化吸入布地奈德0.25 mg进行治疗;观察组患儿在此治疗基础上口服孟鲁司特钠5 mg,每日1次进行治疗。采用酶联免疫吸附实验分别在患儿入院次日和治疗7 d后,检测血清白细胞介素-8、嗜酸粒细胞阳离子蛋白、半胱氨酰白三烯水平;同时观察治疗后两组患儿症状消失时间及不良反应发生情况。结果:与治疗前相比,所有患儿白细胞介素-8、嗜酸粒细胞阳离子蛋白、半胱氨酰白三烯水平均明显降低(P0.05),其中观察组更显著(P0.05)。观察组患儿咳嗽、憋喘、呼吸困难、气促症状的消失时间均短于对照组(P0.05);不良反应发生率也明显低于对照组(P0.05)。结论:孟鲁司特钠对呼吸道合胞病毒感染的毛细支气管患儿具有明显的疗效和良好的安全性。     

呼吸道合胞病毒感染患儿免疫功能变化及PBL体外表达IL－2R的动态观察

探讨７２例确诊呼吸道合胞病毒（ＲＳＶ）特异性血清抗体及鼻咽分泌物脱落细胞中ＲＳＶ抗原阳性患儿急性期及恢复期Ｔ淋巴细胞亚群，血清ＩｇＧ、ＩｓＭ、ＩｇＡ及ＩＬ－２Ｒ的活性表达，动态观察了呼吸道合胞病毒感染患儿急性期、恢复期和正常对照组外周血淋巴细胞经ＰＨＡ刺激后，于不同时间（２４ｈ、４８ｈ、７２ｈ）细胞膜上ＩＬ－２Ｒ的活性表达。结果表明，抗体效价恢复期较急性期升高４～１２８倍，病例组急性期ＣＤ３、ＣＤ１６、Ｂ细胞升高，ＣＤ４／ＣＤ８的比值下降，ＩｇＧ、ＩｇＡ均降低，而ＩＬ－２Ｒ的活性表达呈下降趋势。此结果有助于探讨ＲＳＶ感染患儿的免疫紊乱发生机制。     

白三烯受体拮抗剂治疗和预防呼吸道合胞病毒毛细支气管炎及感染后反复喘息的临床观察

目的观察白三烯受体拮抗剂（孟鲁司特）治疗和预防呼吸道合胞病毒（RSV）毛细支气管炎及感染后反复喘息的发生。方法选择2008年11月～2010年02月我院收治的RSV毛细支气管的住院患儿104例,随机分为治疗组（52例）和对照组（52例）,在相同的综合治疗基础上,对照组常规使用激素和用布地奈德、异丙托溴铵、沙丁胺醇悬液雾化吸入,治疗组同时予孟鲁司特4mgpoqn,连用4周,观察急性期喘憋、呼吸困难、咳嗽、肺部喘鸣音消失时间,平均治疗天数及随访1月内喘息再发情况。结果两组比较差异均有统计学差异。结论应用白三烯受体拮抗剂（孟鲁司特）治疗RSV毛细支气管炎,可以明显缩短急性期病程,减少日后反复发作的喘息。     

呼吸道合胞病毒感染患儿免疫功能变化及PBL体外表达IL—2R的…

探讨７２例确诊呼吸道合胞病毒特异性血清抗体及鼻咽分泌微生物 脱落细胞中ＲＳＶ抗原阳性患儿急性期及恢复期Ｔ淋巴细胞亚群，血清ＩｇＧ，ＩｇＭ，Ｉｇ及ＩＬ－２Ｒ的活性表达，动态观察了呼吸道合胞病毒感染患儿急发型型，恢复期和正常对照组外周血淋巴细胞以ＰＨＡ刺激后，于不同时间细胞膜上ＩＬ－２Ｒ的活性表达。     

Production of interferon gamma in respiratory syncytial virus infection of humans is not associated with interleukins 12 and 18

In order to understand early events in the immune response to respiratory syncytial virus (RSV) infection, we studied the presence of various chemokines and cytokines in respiratory secretions of human infants with RSV infection. Interferon gamma (IFNgamma) was present in 30/39 (76.9%) subjects tested, but the IFNgamma-inducing cytokines interleukin (IL)12 and IL18 were detectable in 6/40 (15%) and 11/38 (28.9%) subjects, respectively. Quantities of IL12 and IL18 did not correlate with those of IFNgamma. IL18, but neither IFNgamma nor IL12 was found in significantly greater concentrations in subjects with mild, nonhypoxic forms of bronchiolitis than in those with upper respiratory illness alone or hypoxic bronchiolitis. The findings suggest that IFNgamma may be induced independently of the activities of IL12 and IL18 during RSV infection. Immune responses characterized by relatively greater release of IL18 may be associated with milder forms of bronchiolitis.     

慢性心力衰竭大鼠模型TNF-α、IFN-γ、IL-4和IL-10的表达

目的：检测慢性心力衰竭病程肿瘤坏死因子α（tumor necrosis factorα,TNF-α）、干扰素-γ（inter-feron-γ,IFN-γ）、白细胞介素-4（interleukin-4,IL-4）和白细胞介素-10（interleukin-10,IL-10）水平的动态变化,以期探讨慢性心力衰竭过程免疫系统状况变化。方法：采用纯种Wistar大鼠作为实验动物,分为正常对照组、假手术组和模型组,每个亚组均10只。采用腹主动脉结扎方法制作慢性心力衰竭模型。术后每两周行超声心动图、血液动力学检测,并取静脉血放射免疫分析进行TNF-α、IFN-γ、IL-4和IL-10的检测。结果：腹主动脉结扎后3月内是心功能代偿期,6月时是心功能失代偿期。在心力衰竭进程中,TNF-α和IFN-γ先降低后升高,IL-4和IL-10水平先升高后降低。结论：心力衰竭的不同进程,免疫机制发生变化,心功能代偿期以体液免疫为主,心功能失代偿期以细胞免疫为主。     

Occurrence and severity of infections caused by subgroup A and B respiratory syncytial virus in children in southeast Brazil

The frequency and severity of infections caused by respiratory syncytial virus (RSV) were assessed in children <2 years of age seen at the emergency department. The frequency of RSV detection in the clinical virology laboratory during the past 3 years was also analyzed retrospectively. RSV was found in 21.6% (188/869) of the samples collected from children seen at the emergency department and was found to be more frequent during the autumn, being less frequent or negligible by midwinter. RSV subgroups A and B co-circulated within the same time period in children seen at the emergency department, with varying predominance of either subgroup. There was no significant association of RSV subgroup with disease severity, but only a trend for RSV subgroup B being more frequent in children with risk factors for severe disease.     

Differentiation and immune function of human dendritic cells following infection by respiratory syncytial virus

RSV causes annual epidemics of bronchiolitis in winter months resulting in the hospitalization of many infants and the elderly. Dendritic cells (DCs) play a pivotal role in coordinating immune responses to infection and some viruses skew, or subvert, the immune functions of DCs. RSV infection of DCs could alter their function and this could explain why protection after natural RSV infection is incomplete and of short duration. In this study, this interaction between DCs and RSV was investigated using a human primary culture model. DCs were generated from purified healthy adult volunteer peripheral blood monocytes. Effects of RSV upon DC phenotype with RSV primed DCs was measured using flow cytometry. Changes to viability and proliferation of cocultured DCs and T-cells were determined using microscopy with fluorescent dyes (Hoechst 33342 and propidium iodide). DC maturation was not prevented by the RSV challenge. RSV infected a fraction of DCs (10-30%) but the virus replicated slowly in these cells with only small reduction to cell viability. DCs challenged with RSV stimulated T-cell proliferation less well than lipopolysaccharide. This is the first study to demonstrate RSV infection of human monocyte derived DCs and suggests that the virus does not significantly interfere with the function of these cells and potentially may promote cellular rather than humoral responses.     

The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis

Neutrophils are the predominant inflammatory cell in the lung tissues and airways in RSV infection, and can augment the epithelial cell damage induced by RSV. Neutrophil apoptosis has been suggested to be a mechanism to reduce the potential for tissue injury. The apoptosis of neutrophils from nasopharyngeal aspirates (NPA) (n = 19) and peripheral blood (PB) of infants with RSV bronchiolitis (n = 11) and PB from healthy controls (n = 9) was investigated. Monoclonal antibody against CD95 (Fas) and a binding protein Annexin V were used to determine the apoptosis of neutrophils. The expression of CD11b and CD18 on neutrophils was also detected with flow cytometry. The mean fluorescence intensity (MFI) of CD95 on neutrophils from RSV⁺ NPA was increased compared with cells from control PB (73.6 ± 7.6 versus 31.5 ± 4.3); the MFI of Annexin V, CD11b and CD18 on neutrophils from RSV⁺ NPA was up-regulated compared with cells from both control PB (105.3 ± 18.1 versus 11.8 ± 1.5; 1683 ± 153.3 versus 841.1 ± 72.3; 517 ± 50.5 versus 147 ± 8.7, respectively) and RSV⁺ PB (105.3 ± 18.1 versus 35.8 ± 4.1; 1683 ± 153.3 versus 818 ± 141.2; 517 ± 50.5 versus 260 ± 25.8, respectively). Furthermore, the percentage of neutrophils expressing Annexin V and the MFI of CD18 on neutrophils from RSV⁺ PB were increased compared with neutrophils from control PB. In addition, both CD11b (MFI) and CD18 (MFI) correlated with Annexin V (MFI) on neutrophils. We conclude that neutrophil apoptosis in RSV bronchiolitis is accelerated; and CD11b/CD18 may play an important role in RSV infection by influencing neutrophil apoptosis.     

Severe respiratory syncytial virus infections and reduced interferon-gamma generation in vitro

To study the consequences of the interaction of respiratory syncytial virus (RSV) with dendritic cells in vitro, we established a model of the primary immune response using dendritic cells, autologous naive T cells and the superantigen toxic shock syndrome toxin 1 (TSST 1). About 10% of the naive T cells express the T cell receptor chain Vbeta2. These cells were stimulated by TSST 1 and could be analysed by flow cytometry. Cultures infected with RSV produced significantly less interferon-gamma compared to uninfected cultures. In a first set of experiments we evaluated whether this culture model using isolated CD4(+) CD45RA(+) T cells, in fact, reflects the primary immune response. In a prospective study, cells were isolated from 13 children at birth, at 1 year of age and at 4 years of age. RSV reduced interferon-gamma production at all the age groups analysed and the results were stable over time within a given individual. In a second set of experiments, we asked whether clinical differences in the course of RSV infection are due to variations in the cellular immune response. At the age of 1 year (5-9 months after the RSV epidemic) dendritic cells and naive T cells were obtained from 27 children with a history of bronchiolitis, from 15 children with a benign course of RSV infection and from 26 controls without RSV infection. The frequency of interferon-gamma-producing cells in RSV infected cultures was significantly lower (P < 0.001) in cultures from children with a history of RSV bronchiolitis compared to children with mild RSV infection. Cultures from children without infection displayed a wide range of results. Overall, interferon-gamma generation in this group was still lower (P < 0.05) than in the group with mild RSV infection. Because we have ruled out that memory cells play a role in the experiments performed, the most likely explanation for our results is that a high generation of interferon-gamma in the primary immune response protects from severe RSV mediated disease.     

Specific increase in local IL-17 production during recovery from primary RSV bronchiolitis

Although Respiratory syncytial virus (RSV) bronchiolitis is the most important cause of hospital admission for infants during the winter season, the pathogenesis is largely unknown. Interleukin‐17 (IL‐17) concentrations were studied in nasopharyngeal aspirates from 21 non‐ventilated and 17 ventilated infants admitted to hospital with RSV bronchiolitis at time of admission and discharge from the hospital. On admission, nasopharyngeal concentrations of most cytokines and chemokines were lower in non‐ventilated infants than in ventilated infants, reaching statistical significance for Eotaxin, IL‐1α, and IL‐6. During course of disease, nasopharyngeal concentrations of most cytokines and chemokines decreased, reaching statistical significance for IL‐6 and IP‐10. However, nasopharyngeal IL‐17 concentrations were higher at discharge than at admission in children with non‐ventilated RSV disease (209–101 pg/ml, P = 0.008), a response pattern not observed in ventilated RSV patients nor for other cytokines or chemokines. It is speculated that local IL‐17 production may be involved during convalescence from RSV bronchiolitis in non‐ventilated patients by facilitating innate and adaptive antiviral immune responses. The role of IL‐17 in the pathogenesis of RSV bronchiolitis is to be explored further. J. Med. Virol. 84: 1084–1088, 2012. © 2012 Wiley Periodicals, Inc.