变应性鼻炎患者血清IL-17和IL-23的表达及临床意义

目的:检测变应性鼻炎(Allergic rhinitis,AR)患者血清IL-17和IL-23的表达水平并探讨其临床意义。方法:检测25例AR患者(观察组)血清IL-17、IL-23、s Ig E(过敏原特异性Ig E)的表达水平,并以23名健康体检合格者(对照组)为对照,比较两组人群血清中IL-17、IL-23、s Ig E表达水平的差异,并探讨AR患者血清中IL-17、IL-23、s Ig E三者间的相互关系。结果:观察组患者血清中IL-17、IL-23及s Ig E水平均高于对照组(P均0.01);观察组患者血清中IL-17、IL-23、s Ig E三者两两之间均呈线性正相关关系(P均0.05)。结论:IL-17、IL-23参与了AR的发生发展过程,与s Ig E的形成可能有关。     

TNF-α、IL-10在变应性鼻炎中的作用研究

目的 通过检测变应性鼻炎(AR)患者血清TNF-α、IL-10在治疗前后的表达变化,探讨二者在变应性鼻炎中的作用.方法 收集33例正常健康对照组以及48例变应性鼻炎患者行脱敏治疗前后的血清标本,应用双抗体夹心ELISA方法测定血清中TNF-α、IL-10的表达水平,SPSS12.0软件进行统 计学分析.结果 TNF-α在AR患者血清中高表达,与对照组相比差异具有统计学意义(P =0.0028),脱敏治疗后其表达下降,治疗前后相比有统计学差异(P =0.0032);IL-10在患者血清中表达低于对照组,差异具有统计学意义(P=0.018),脱敏治疗后其表达上升,与治疗前相比差异有统计学意义(P=0.024);TNF-α、IL-10在AR患者中的表达呈负相关(r=-0.413,P＜0.05).结论 TNF-α和IL-10在变应性鼻炎发病过程中可能起到重要作用.     

IL-23/IL-17轴在银屑病免疫发病机制中的作用

银屑病是一种以T淋巴细胞异常活化和浸润为主要特征的慢性炎性反应皮肤病。Th17细胞及IL-23/IL-17轴在银屑病的发病机制中可能处于关键地位,并成为新的治疗靶标。IL-23诱导Th17细胞分化增殖,分化成熟的Th17可以分泌IL-17、IL-21、IL-22等多种细胞因子,Th17类细胞因子在银屑病等多种自身免疫疾病和炎性疾病中起重要作用。     

IL-23在慢性乙型肝炎免疫调节中的作用研究

目的 探讨IL-23在慢性乙型肝炎免疫调节中的作用。方法 选取我院收治的32例HBeAg阳性慢性乙型肝炎患者为研究对象,根据ALT水平分为ALT≥120 IU/ml患者16例,ALT＜120 IU/ml患者16例,另外选择我院健康体检中心20例体检者作为健康对照组,采用酶联免疫分析法（ELISA）检测血清IL-23水平,采用流式细胞仪检测Th17细胞百分率。结果 与健康对照组相比,HBeAg阳性慢性乙型肝炎患者血清IL-23表达及外周血Th17细胞百分率均升高,差异有统计学意义（P＜0.05）; ALT≥120 IU/ml患者血清IL-23浓度（394.81±101.84）pg/ml高于ALT＜120IU/ml的（283.69±85.65）pg/ml,ALT≥120 IU/ml患者Th17细胞百分率（3.25±0.70）%高于ALT＜120IU/ml的（2.68±0.61）%,差异均有统计学意义（P＜0.05）;慢性乙型肝炎患者外周血Th17细胞百分率、血清IL-23浓度与ALT程度呈正相关（P均＜0.05）;Th17细胞百分率与血清IL-23浓度呈正相关（P＜0.05）。结论 IL-23可能通过影响Th17细胞的免疫调节参与慢性乙型肝炎患者炎症,为临床提供了新的靶标。     

Th17细胞在小鼠变应性鼻炎鼻黏膜中的表达及意义

目的：探讨T辅助细胞17(Th17)在小鼠变应性鼻炎鼻黏膜中的表达及意义。方法：以卵清蛋白致敏的Balb/c小鼠变应性鼻炎模型作为实验组,同期以生理盐水替代作为对照组。取两组小鼠鼻黏膜,制成单细胞悬液,使用流式细胞仪检测两组小鼠鼻黏膜中Th17细胞比例。结果：两组小鼠鼻黏膜中均存在Th17细胞,并且实验组中Th17比例[(1.27±0.138)%与(0.771±0.088)%]高于对照组,差异具有统计学意义(P<0.05)。结论：明确变应性鼻炎鼻黏膜中Th17细胞比例,为变应性鼻炎的治疗提供理论依据以及新思路。     

变应性鼻炎和哮喘患者血清IL-5、IL-15及IL-18的水平研究

目的探讨IL-5、IL-15和IL-18在变应性鼻炎、支气管哮喘、变应性鼻炎合并哮喘疾病中的作用。方法采用双抗体夹心ELISA测定法对33例支气管哮喘患者、35例变应性鼻炎患者、35例变应性鼻炎合并哮喘的患者及35例正常健康查体者血清中IL-5、IL-15和IL-18的水平进行检测。结果支气管哮喘、变应性鼻炎、变应性鼻炎合并哮喘的患者血清中IL-5、IL-15和IL-18水平较正常对照组升高（P〈0．01）,IL-5、IL-15,IL-18水平在变应性鼻炎合并哮喘组均高于鼻炎组与和哮喘组;鼻炎组IL-5水平高于哮喘组（P=0．003）,哮喘组IL-18水平高于鼻炎组（P=0．001）。结论IL-5、IL-15和IL-18参与了过敏性鼻炎和哮喘的发病过程;变应性鼻炎合并哮喘的炎症程度较高;哮喘和鼻炎因发病部位不同炎症反应也有不同。     

白介素17单克隆抗体对变应性鼻炎小鼠气道炎症的作用

目的 探讨白介素17单克隆抗体（IL-17mAb）的不同给予剂量及方式在变应性鼻炎小鼠气道炎症中的作用。方法 将48只小鼠采用随机数字表法分为A、 B、 C、 D、 E、 F组,每组8只。分别于第0、 7、 14 d将20 μg卵清蛋白（OVA）加2 mg铝佐剂腹腔注射处理A、C、D、E及F组小鼠,间隔7 d,第22天开始进行鼻腔激发,每天每侧鼻孔各给予OVA 10 μl（共500 μg）滴鼻,连续7 d。A、C、D、E组小鼠于每次OVA鼻腔激发前1 h分别给予生理盐水、100 ng IL-17mAb、500 ng IL-17mAb、5 μg IL-17mAb滴鼻,F组小鼠于每次OVA鼻腔激发前4 h给予5 μg IL-17mAb腹腔注射,B组小鼠于相同时间点给予等量生理盐水腹腔注射及滴鼻。所有小鼠于最后1次激发后评估鼻部症状学变化,Diff-Quik染色观察鼻腔灌洗液（NLF）中嗜酸性粒细胞浸润情况,ELISA方法检测血清及NLF中IL-6、IL-10水平,鼻黏膜组织行甲苯胺蓝染色观察肥大细胞。结果 ４周末A组所有小鼠症状学评分均＞5分,提示造模成功。F组小鼠的挠鼻及喷嚏次数均少于A组（P＜0.05）;F组小鼠NLF中嗜酸性粒细胞数、血清IL-6水平低于A组,血清及NLF中IL-10水平均高于A组（P＜0.05）;E组小鼠血清中IL-10水平高于A组（P＜0.05）;A组小鼠鼻黏膜组织中肥大细胞数多于B组,统计学意义显著（P＜0.01）;F组小鼠鼻黏膜组织中肥大细胞数少于A组,但差异无统计学意义（P＞0.05）;F组小鼠鼻黏膜组织中肥大细胞数与B组比较,差异无统计学意义（P＞0.05）。结论 高剂量的（5 μg）IL-17mAb腹腔注射处于激发阶段的变应性鼻炎小鼠促使小鼠变应性鼻炎症状明显减轻,鼻腔灌洗液嗜酸性粒细胞减少。促使变应性鼻炎小鼠血清中IL-6表达降低,血清中及鼻腔灌洗液中IL-10表达升高,因此推测这些细胞因子的变化可能抑制Th17/促进Treg的分化,进而对变态反应产生抑制作用。     

IL-17A抗体抑制变应性鼻炎鼠模型中IL-17A及RORγt并升高Foxp3 mRNA表达

目的：探讨IL-17A抗体对小鼠变应性鼻炎鼻黏膜中IL-17A、RORγt、Foxp3 mRNA水平的影响及意义。方法：以卵清蛋白致敏的Balb/c小鼠变应性鼻炎模型作为实验组,同期以生理盐水替代作为对照组,使用IL-17A抗体治疗作为治疗组。实时定量PCR方法检测三组小鼠鼻黏膜中IL-17A、RORγt、Foxp3mRNA的含量。结果：实验组中RORγt以及IL-17AmRNA水平均较对照组升高(P<0.05),治疗组中RORγt以及IL-17AmRNA的含量均低于实验组(P<0.05)。而实验组中Foxp3 mRNA水平较对照组下降(P<0.05),治疗组中Foxp3 mRNA的含量高于实验组(P<0.05)。结论：IL-17A抗体抑制变应性鼻炎鼠模型中IL-17A及RORγt mRNA水平并升高Foxp3 mRNA表达水平。     

IL-35抑制炎症反应和T细胞反应性减轻变应性鼻炎的机制研究

目的：探讨IL-35在变应性鼻炎中对炎症反应和T细胞反应性的作用及其机制。方法：选取2012年1月至2016年1月间本院收治的37例变应性鼻炎患者（观察组）及35例行变应性鼻炎过敏原检测后排除变应性鼻炎的健康志愿者（对照组）为研究对象,采集观察组和对照组的外周血液,ELISA检测患者血清中IL-35水平。建立小鼠变应性鼻炎动物模型,收集小鼠外周血液,ELISA检测小鼠血清中IL-35及IgE水平。小鼠鼻切片后组织染色检测嗜酸性粒细胞;分离小鼠脾脏细胞后加入卵清蛋白抗原,加入或不加入IL-35至培养基中,检测卵清蛋白特异性T细胞反应性;ELISA检测T细胞培养上清中细胞因子IL-2、IL-4、IL-5、IL-10、IL-13,IL-17、 IL-23、IL-27以及TNF-α含量;荧光定量PCR（Real-time PCR）检测培养T细胞中IL-2、IL-4、IL-5、IL-10、IL-13、IL-17、IL-23、IL-27以及TNF-α mRNA表达水平;Western blot 检测培养T细胞JNK、Erk1/2及p38信号途径的激活水平。结果：观察组血清IL-35水平显著低于对照组（P＜0.05）;变应性鼻炎组小鼠组织染色结果显示嗜酸性粒细胞浸润数量显著高于正常组（P＜0.05）,而血清IL-35水平则显著低于正常小鼠（P＜0.05）; 卵清蛋白特异性T细胞反应性检测显示IL-35能显著抑制其反应性;ELISA及Real-time PCR结果均显示,IL-35能够显著下调IL-4、IL-5、IL-13、IL-17、IL-23及TNF-α的表达,上调IL-2、IL-10及IL-27的表达。Western blot结果显示,IL-35能够显著抑制卵清蛋白特异性T细胞中JNK、Erk1/2及p38信号途径的激活水平。结论：IL-35能够调控炎症反应中的炎症因子表达和T细胞的反应性,从而减轻变应性鼻炎,其机制可能是通过调控JNK、Erk1/2及p38信号途径的激活水平。     

Effects of lysedEnterococcus faecalis FK-23 on experimental allergic rhinitis in a murine model

In the current study,we sought to investigate whether lysed Enterococcus faecalis FK-23(LFK),a heat-killed probiotic preparation,attenuated eosinophil influx into the upper airway and had immunomodulatory activity in a murine allergic rhinitis model.Eighteen BALB/c mice were divided into three groups;the ovalbumin(OVA)-sensitized/challenged group,which received saline orally for 6 weeks(OVA group),the OVA-sensitized/challenged group,which received LFK orally for 6 weeks(LFK-fed group),and the non-sensitized group,which received saline for 6 weeks(saline control group).Nasal rubbing and sneezing were monitored during the study.After the final challenge,interleukin(IL)-4,interferon(IFN)-γ,and OVA-specific IgE levels in the sera and splenocyte culture supernatants were determined,eosinophilic infiltrate into the upper airway was quantified,and splenic CD4+CD25+ regulatory T cells(Tregs) were examined by flow cytometry.We found that nasal rubbing was significantly reduced in LFK-fed mice compared to the OVA group on d 27 and 35,and sneezing was significantly inhibited by LFK administration for 35 d.LFK-fed mice had significantly less eosinophil influx into the nasal mucosa than the OVA group.There were no significant differences between the LFK-fed group and OVA group in the serum and splenocyte culture supernatant levels of IL-4,IFN-γ,and OVA-specific IgE.Interestingly,the LFK-fed mice had a significantly greater percentage of splenic CD4+CD25+ Tregs than OVA group.Our results indicate that oral administration of LFK may alleviate nasal symptoms,reduce nasal eosinophilia,and increase the percentage of CD4+CD25+ Tregs in experimental allergic rhinitis.     

Up-regulation of IL-18 in allergic rhinitis

BACKGROUND: This paper reports a study on the concentrations of the pro-inflammatory cytokines IL-18 and IL-1beta in nasal secretions of allergic rhinitis patients in relation to ECP and nasal symptoms. METHODS: We measured IL-18 and IL-1beta concentrations using ELISA, and eosinophilic cationic protein (ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis (SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal and ocular symptoms were monitored daily. Furthermore, we measured IL-18, IL-1beta and ECP concentrations in nasal secretions of 19 controls and 20 symptomatic persistent allergic rhinitis (PAR) patients with house dust mite allergy. RESULTS: In SAR, the increase of IL-18, IL-1beta and ECP paralleled the pollen flight with a time delay. IL-18 and IL-1beta significantly increased during the pollen season compared to baseline, and differently from ECP, remained elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and ECP, but not IL-1beta, were significantly higher compared to controls, with IL-18 concentrations also being significantly higher than in SAR. CONCLUSION: This is the first study to demonstrate the up-regulation of IL-18 in nasal secretions in allergic rhinitis. The persistence of elevated IL-18 concentrations until after the season and the high concentrations in PAR compared to SAR suggests its role in persistent allergic inflammation.     

变应性鼻炎患者血清IL-33和可溶性ST_2检测的临床意义

为研究IL-33在变应性鼻炎发病机制中的作用,我们采用ELISA法检测了62例变应性鼻炎和49例健康者血清IL-33以及sST2水平,并分析了血清IL-33与变应性鼻炎患者临床特征的关系。结果发现变应性鼻炎患者血清IL-33水平较健康者显著增高(P0.01),sST2水平则较健康者显著降低(P0.01)。持续性和间歇性变应性鼻炎患者IL-33和sST2水平相当。IL-33与变应性鼻炎患者TNSS评分、嗜酸粒细胞计数和血清总IgE呈正相关(P均小于0.01)。研究结果表明IL-33反应增强是变应性鼻炎的特征之一。IL-33可能通过调节Th2细胞而参与了变应性鼻炎的发病机制。     

变应性鼻炎病人IL-4、IL-5和GM-CSF的水平观察

变态反应性鼻炎的发病机理与诸多细胞因子有关的现象，近年来已越来越受到国内外学者的重视[1］。变态反应性鼻炎发作时细胞因子的产生及炎性介质的参与均与机体异常的免疫调节有关，即存在T辅助细胞（TH）亚群功能失调，通过释放细胞因子，促进IgE的合成与分泌，并增加炎症细胞的浸润和活化。本文观察变应性鼻炎病人血清IL-4、IL-5和GM-CSF水平变化，为变应性鼻炎的防治提供依据。1材料与方法1. 1研究对象实验组为本院变态反应专科门诊确诊为尘螨变应性鼻炎（1997年修订，海口，变应性鼻炎诊断标准）病人86例，其中男性46例，女性40…     

Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis

BACKGROUND: Sublingual immunotherapy (SLIT) is a clinically effective treatment in both pollen and house dust mite-induced rhinitis and asthma. However, the mechanisms by which this is accomplished are not clear. OBJECTIVE: The objective of the current study was to establish a mouse model of rhinitis in order to study the effect and mechanisms of SLIT. METHODS: Mice were sensitized by intraperitoneal injections of alum-adsorbed Phleum pratense extract. Sensitized mice were SLIT-treated and subsequently challenged intranasally and analysed for clinical symptoms, antibody levels, eosinophilia and T cell response. RESULTS: Intranasal challenge of sensitized mice led to the development of rhinitis characterized by significantly increased sneezing and influx of eosinophils into the nose. Levels of specific IgE were fivefold increased in nasopharyngeal lavage (NAL) fluid and more than doubled in serum. Furthermore, a T-helper type 2 (Th2) like T cell response was observed in local draining lymph nodes. SLIT treatment of sensitized mice reduced sneezing, eosinophilia and IgE levels in the NAL by more than 50%. Moreover, serum levels of IgE and IgG1 as well as T cell response in the draining lymph nodes were also significantly reduced. Treatment for a shorter time or with a lower dose only led to minor reductions of the clinical and immunological parameters, indicating that the effect of SLIT is time and dose dependent. CONCLUSION: In the present study, we have established a mouse model displaying the hallmarks of allergic rhinitis using a clinically relevant allergen. Using this model, we have demonstrated that SLIT treatment is able to reduce allergic symptoms in a time- and dose-dependent manner.