不同证型变应性鼻炎外周血清中维生素D、IL-4及 IFN-γ水平比较

目的 探讨血清1,25羟维生素D3、血清IL-4、IFN-γ水平与不同中医证型变应性鼻炎（AR）的相关性。方法 应用高效液相色谱串联质谱仪测定4组不同中医证型变应性鼻炎患者各30例及30例正常体检患者血清1,25羟维生素D3,ELISA酶联免疫法测定各组血清IL-4、IFN-γ水平。结果 4种不同中医证型的变应性鼻炎组血清1,25羟维生素D3、血清IFN-γ水平低于健康对照组,而血清IL-4水平则高于健康对照组,差异具有统计学意义（P＜0.05）;不同证型的变应性鼻炎患者之间三种因子水平比较,差异无统计学意义（P＞0.05）。结论 血清1,25羟维生素D3缺乏或不足与变应性鼻炎具有密切的关系,其可能作用机制为血清1,25羟维生素D3缺乏可导致机体Th1/Th2细胞因子分泌失衡,刺激IgE水平升高引起变态反应。不同证型的变应性鼻炎患者血清1,25羟维生素D3、血清IL-4、IFN-γ水平大致相当。     

IgE、IFN-γ和IL-8在过敏性鼻炎患者血清中的表达及临床意义

目的 探讨IgE、IFN-γ和IL-8在过敏性鼻炎患者血清中的表达及临床意义。方法 选取2018年1月至2020年12月于我院就诊的110例过敏性鼻炎患者纳入观察组,按照患者病情严重程度,将其分为轻度组(41例)、中重度组(69例)。另选取50例体检健康者纳入对照组,采用ELISE法检测各组血清IgE、IFN-γ和IL-8水平,比较轻度组、中重度组过敏性鼻炎评分量表(SFAR)及视觉模拟量表(VAS)评分,分析IgE、IFN-γ和IL-8水平与各量表评分的相关性。结果 与对照组比较,观察组血清IgE和IL-8水平明显较高,而IFN-γ水平明显较低(P<0.05);与轻度组比较,中重度组血清IgE和IL-8水平明显较高,而IFN-γ水平明显较低(P<0.001);与轻度组比较,中重度组SFAR量表及VAS量表评分明显较高(P<0.001);血清IgE、IL-8水平与SFAR量表及VAS量表评分呈正相关(P<0.001);血清IFN-γ水平与SFAR量表及VAS量表评分呈负相关(P<0.001);IgE诊断过敏性鼻炎的AUC为0.819(95%CI:0.749...     

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。     

艾叶挥发油治疗大鼠变应性鼻炎的实验研究

目的:观察艾叶挥发油对变应性鼻炎(AR)大鼠血清中IgE、IL-4和IL-5含量的影响。方法:60只SD大鼠按体重随机分为正常对照组、模型组、治疗组和阳性药对照组,每组10只。实验组用卵蛋白(OVA)、氢氧化铝和灭活百日咳杆菌皮下注射致敏,用10%的卵蛋白生理盐水溶液滴鼻激发,建立AR模型。正常对照组以等量生理盐水代替。治疗组和阳性药对照组分别灌胃给予艾叶挥发油和氯雷他定治疗10天,正常对照组用橄榄油代替药物;另外20只大鼠用于被动皮肤过敏原试验(PCA),检验大鼠模型制备及治疗情况;用ELISA法测定各组大鼠外周血清IL-4、IL-5和IgE含量。结果:模型组大鼠鼻喷嚏平均次数明显多于正常对照组、治疗组和阳性对照组(P<0.05);模型组大鼠PCA试验阳性率为92%,其余三组全部表现为阴性;模型组IgE均显著高于正常对照组(P<0.05);治疗组IgE、IL-4、IL-5均显著低于模型组(P<0.05);治疗组各项指标与阳性对照组比较差异无统计学意义。结论:艾叶挥发油可降低AR大鼠血清中IL-4、IL-5和IgE含量,减轻鼻粘膜变应性炎症。     

鼻炎清颗粒治疗变应性鼻炎的免疫机制研究

目的:观察鼻炎清颗粒治疗大鼠变应性鼻炎(AR)后,细胞因子、血清特异性IgE和嗜酸粒细胞阳离子蛋白(ECP)的水平,了解该药治疗AR的部分免疫学机制.方法:用卵清蛋白(OVA)、氢氧化铝、百白破疫苗联合致敏大鼠建立变应性鼻炎动物模型,鼻炎清颗粒灌胃给药2周后,观察鼻黏膜组织学变化,ELISA法检测血清细胞因子IL-4、 IFN-γ、 IgE 和ECP的水平.结果:光镜观察发现,模型组鼻黏膜上皮细胞脱落、水肿、血管扩张、腺体增生,固有层内可见大量嗜酸性粒细胞、肥大细胞浸润,治疗组大剂量和中剂量组及阴性对照组则无上述改变.治疗组大、中剂量组血清IL-4水平分别为(10.30±4.41) ng/L 和(12.42±6.55) ng/L,明显低于模型组(17.62±6.10) ng/L,有统计学差异(P＜0.01或P＜0.05);而IFN-γ水平分别为(34.19±6.16) ng/L和(27.92±6.47) ng/L,明显高于模型组(19.33±5.63) ng/L(P＜0.01);3种剂量组的血清IgE水平分别为(26.46±6.12) μg/L、 (49.11±4.48) μg/L和(70.68±7.59) μg/L,与阳性模型组(81.03±7.54) μg/L,相比较有统计学差异(P＜0.01或P＜0.05);血清ECP水平分别为(1.48±0.25) μg/L,(2.30±0.56) μg/L和(3.05±1.27) μg/L,与阳性模型组(4.23±1.20) μg/L比较,大、中剂量组有统计学意义(P＜0.01或P＜0.05),小剂量组无统计学意义.结论:鼻炎清颗粒通过调节Th1和Th2细胞因子的表达,纠正失衡的Th1/Th2的细胞因子网络,降低血清特异性IgE和ECP水平和抑制炎症细胞在鼻黏膜的聚集,防止其脱颗粒,对变应性鼻炎产生治疗作用.     

氯雷他定联合孟鲁司特钠辅助布地奈德治疗对变应性鼻炎患者炎性细胞及因子表达水平的影响分析

目的 研究氯雷他定联合孟鲁司特钠辅助布地奈德对老年季节性变应性鼻炎患者鼻腔EOS阳性率、IgE及炎性因子水平的影响.方法 选择2014年1月至2015年12月在我院接受治疗的老年季节性变应性鼻炎患者160例.用随机数表法分为对照组和实验组,每组各80例,对照组患者给予布地奈德鼻喷剂治疗,实验组患者在对照组的基础上加用氯雷他定和孟鲁司特钠治疗.比较两组患者的症状评分、鼻腔EOS阳性率、血清特异性IgE和血清炎性因子水平.结果 治疗后两组患者的鼻塞、流涕、鼻痒、喷嚏症状评分明显降低,实验组患者的以上评分低于对照组(P＜0.05).治疗后两组患者的鼻腔EOS阳性率和血清特异性IgE水平明显下降,实验组患者的鼻腔EOS阳性率和血清特异性IgE水平低于对照组(P＜0.05).治疗后两组患者的IL-6、IL-8水平明显降低,IL-10水平升高,实验组患者的炎性因子水平变化更明显(P＜0.05).两组患者在治疗过程中未见明显不良反应,治疗后4周肝、肾功能正常.结论 氯雷他定联合孟鲁司特钠辅助布地奈德可以明显缓解老年季节性变应性鼻炎患者的症状,降低血清特异性IgE及鼻腔内分泌EOS阳性率,减轻炎症反应.     

变应性鼻炎大鼠动物模型的建立及评价

目的建立和评价SD大鼠变应性鼻炎模型。方法将SD大鼠随机分为对照组和模型组,模型组给予卵白蛋白(OVA)配合佐剂氢氧化铝全身致敏和局部致敏,建立SD大鼠变应性鼻炎模型;对照组以生理盐水代替OVA;HE染色检测鼻粘膜组织形态学变化;Wright’s染色检测模型组鼻腔分泌物和鼻粘膜组织嗜酸性粒细胞的表达;酶联免疫吸附测定法(ELISA)检测外周血IgE水平;通过行为学总积分对动物模型进行评价。结果模型组鼻粘膜组织纤毛脱落、倒伏,粘膜下腺体数量明显增加;模型组鼻腔分泌物中检测到大量嗜酸性粒细胞;模型组外周血IgE水平较对照组明显增高,具有统计学意义(P0.05);滴鼻后模型组喷嚏、抓鼻的次数及流涕等行为学总积分较对照组组明显增高,具有统计学意义(P0.05)。结论通过卵清蛋白配合佐剂氢氧化铝基础致敏和强化致敏,可成功建立SD大鼠变应性鼻炎动物模型,具有操作简单、重复性好、成功率高的优点,为今后变应性鼻炎的病变研究提供了有效的方法及组织形态学依据。     

罗格列酮对变应性鼻炎小鼠galectin-9、tim-3信号和炎性分子表达的影响

目的研究PPAR-γ激动剂罗格列酮(ROS)对变应性鼻炎小鼠鼻黏膜半乳糖凝集素-9(galectin-9)和T细胞免疫球蛋白黏蛋白分子-3(tim-3)表达的影响。方法应用卵清蛋白(OVA)致敏建立小鼠变应性鼻炎模型,应用免疫组化及Real Time-PCR方法检测ROS对小鼠鼻黏膜中galectin-9和tim-3表达影响,应用ELISA法检测小鼠血清中IL-4、IL-5、IFN-γ含量。结果变应性鼻炎(AR)小鼠鼻黏膜中galectin-9和tim-3表达较正常对照组明显增高,罗格列酮及地塞米松治疗后galectin-9和tim-3的表达降低。与正常对照组比较,变应性鼻炎小鼠血清IL-4、IL-5含量明显升高,而IFN-γ含量明显减低;罗格列酮组和地塞米松组IL-4和IL-5含量较AR组降低,IFN-γ含量上调。结论罗格列酮抑制变应性鼻炎黏膜炎症反应,可能与降低鼻黏膜galectin-9和tim-3的表达相关。     

哮喘灵雾化吸入对哮喘大鼠IFN-γ、IL-4及IgE水平的影响

目的: 探讨哮喘灵雾化吸入对哮喘鼠血清中IFN-γ、 IL-4 和IgE水平的影响及其可能机制.方法: 建立Wistar大鼠哮喘模型, 哮喘灵(27.84 g/kg、 13.92 g/kg)雾化吸入治疗7 d, 用放射免疫法测定血清中IFN-γ、 IL-4及IgE的含量.结果: 与模型组比较, 哮喘灵治疗组大鼠血清IFN-γ水平升高(P＜0.05)、 IL-4和IgE水平下降(P＜0.01), 且药物治疗组大鼠的哮喘症状得到缓解, 引喘潜伏期明显延长.结论: 哮喘灵可通过调节哮喘鼠IFN-γ、 IL-4和IgE的水平而起到治疗哮喘的作用.     

结核分枝杆菌培养滤液蛋白对变应性鼻炎患者Th1和Th2失衡的影响

目的：观察结核分枝杆菌培养滤液蛋白（Mycobacterium tuberculosis culture filtrate protein，CFP）对变应性鼻炎患者Th1和Th2失衡的影响。方法：抽取30例变应性鼻炎患者外周静脉血，分离单个核细胞（PBMCs），采用MTF法测定刺激淋巴细胞增殖最佳CFP浓度，采用酶联免疫吸附试验（ELISA）检测CFP干预前后PBMCs培养上清液中的白细胞介素4（IL-4）、白细胞介素5（IL-5）和干扰素γ（IFN-γ）水平。结果：变应性鼻炎患者组PBMCs上清液中IL-4、IL-5含量较正常对照组显著增高，而IFN-γ含量显著减少。CFP干预后变应性鼻炎患者组上清液IL-4、IL-5水平明显降低，而IFN-γ含量显著升高，差异有显著性。结论：CFP能纠正变应性鼻炎患者体内Th1和Th2细胞因子的失平衡状态，为治疗变应性鼻炎提供了理论依据。     

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。     

血清IL-33、IFN-γ与IgE在支气管哮喘患者中的表达及临床意义

目的观察血清白细胞介素-33(IL-33)、干扰素-γ(IFN-γ)及IgE在支气管哮喘患者中的表达及意义。方法选取94例急性发作期支气管哮喘患者,同时选取同期60例健康体检的人群为对照组,采用酶联免疫法测定血清中IgE、IL-33及IFN-γ水平。比较两组IgE、IL-33和IFN-γ的水平。分析IL-33、IFN-γ和IgE的相关性。结果支气管哮喘患者外周血中IFN-γ水平低于正常人群(t=4.533,P<0.001);IL-33、IgE水平高于正常人群(t=5.831、66.129,P<0.001,<0.001),差异有统计学意义。IgE水平与IL-33水平呈正相关(r=0.667,P=0.032),IFN-γ与IgE、IL-33呈负相关(r=-0.714,P=0.024;r=-0.623,P=0.038)。结论血IgE、IL-33和IFN-γ水平的变化在支气管哮喘患者发病过程中起到一定的作用。     

Immunotherapy Affects the Seasonal Increase in Specific IgE and Interleukin-4 in Serum of Patients with Seasonal Allergic Rhinitis

This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese cedar pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 ± 3.2 years) with immunotherapy using Japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-γ (IFN-γ) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-γ were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-γ was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-γ did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.     

Systemic Administration of Olygodeoxynucleotides with CpG Motifs at Priming Phase Reduces Local Th2 Response and Late Allergic Rhinitis in BALB/c Mice

Oligodeoxynucleotides (ODN) with CpG motifs (CpG ODN) induce T helper (Th)1-type reaction. We aimed to evaluate the therapeutic effect of CpG ODN in the development of late allergic rhinitis induced by ovalbumin (OVA), which is one of Th2 diseaes, in BALB/c mice. Effects of a single dose of synthetic CpG-ODN (50 μg) intraperitoneally (i.p.) at the priming phase (on day 0) by OVA on the development of late eosinophilic rhinitis at respiratory areas were compared to the control mice treated with its vehicle (ODN without CpG motifs; 50 μg). Animals were again sensitized by OVA (on day 10) i.p., and 4 days after second sensitization animals were challenged by OVA intranasally (on day 14). Four days after challenge, eosinophilic reactions, nasal lesions and local cytokine values were examined. Compared to the control group, the CpG ODN-administration increased production of OVA-specific Th1 cytokine (interferon-γ) and decreased productions of ovalubmin-specific Th2 cytokines [interleukin (IL)-5 and IL-13] in nasal cavity fluids, supernatants of splenocytes and/or sera. Also, eosinophilia and increased total IgE values were decreased in mice treated with the CpG ODN compared to the control group. Moreover, nasal lesions with infiltration of eosinophils were prominently reduced by the CpG ODN-treatment compared to the control mice. The present study suggests that the systemic administration of CpG ODN at the priming phase may reduce local OVA-specific Th2 responses, resulting in decreased nasal pathology in the late allergic eosinophilic rhinitis. The authors wish it to be known, in their opinion, Toshiharu Hayashi and Keiko Hasegawa contributed equally to this work.     

新疆维、汉人群变应性鼻炎患者血清IL-4和IFN-γ水平及其与鼻粘膜嗜酸性粒细胞浸润的相关性

目的:探讨新疆维、汉人群变应性鼻炎(Allergic rhinitis,AR)患者血清白细胞介素4(Interleukin-4,IL-4)和干扰素γ(Interferon gamma,IFN-γ)水平与鼻粘膜嗜酸性粒细胞(Eosionphils,EOS)浸润的相关性。方法:采用酶联免疫吸附法(Enzyme-linked immunosorbnent assay,ELISA)测定59例维吾尔族AR患者、50例汉族AR患者外周血清IL-4和IFN-γ水平,高倍显微镜下观察病理涂片并计数AR患者鼻粘膜EOS计数。结果:维、汉人群AR患者血清IL-4和IFN-γ水平均无显著差异(t值分别为1.304和1.408,P均>0.05);维、汉人群AR患者IL-4水平与鼻粘膜嗜酸性粒细胞计数均呈正相关(r分别为0.828和0.691,P均<0.01),IFN-γ水平与鼻粘膜EOS计数均呈负相关(r分别为-0.712和-0.764,P均<0.01)。结论:维、汉人群AR患者的血清IL-4和IFN-γ水平均无显著差异,AR患者鼻粘膜EOS增多与血清IL-4分泌过多而IFN-γ分泌受抑制有关。     

Clinical value of serum IL-27 in allergic rhinitis patients and its relationship with Treg associated cytokine levels

Allergic rhinitis (AR) is a nasal allergic disease mainly mediated by IgE, and the immune response is the pathological basis of AR pathogenesis. Regulatory T cells (Treg) has been confirmed to be involved in the occurrence of AR. IL-27 mediates inflammatory responses and allergic symptoms in AR by promoting Tregs and related factors. Our study aimed to explore the correlation between serum interleukin 27 (IL-27) and Treg associated cytokines in the pathogenesis of AR. Based on the inclusion and exclusion criteria, 69 participants with AR and 50 healthy participants were selected. Their IL-27, IL-10, and TGF-β1 levels were estimated by ELISA. Receiver operating characteristics curve (ROC) was performed to demonstrate the diagnostic efficiency of IL-27 in AR. Pearson correlation analysis was used for correlation analysis. IL-27 in AR patients statistically decreased compared to the control group. Consistently, IL-27 were also negatively correlated with the clinical severity of AR patients. Treg related cytokines including IL-10 and TGF-β1 in AR patients was statistically decreased. In addition, the IL-10 and TGF-β1expressions were positively correlated with IL-27 in AR patients. IL-27 was statistically down-regulated in patients with AR, which is related to insufficient Treg function. Restoring the expression of IL-27 may become a novel approach to treat AR.     

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.