Oral-Antigen Delivery via a Water-in-Oil Emulsion System Modulates the Balance of the Th1/Th2 Type Response in Oral Tolerance

Purpose. To evaluate the ability of a water-in-oil (W/O) emulsion containing ovalbumin (OVA), a model antigen, to induce oral tolerance and to elucidate the mechanism for the induction of oral tolerance by the emulsion system. Methods. A W/O emulsion containing OVA was prepared and evaluated its ability to induce oral tolerance in mice. Also, the Th1/Th2 balance in the mice tolerized was investigated in terms of the ratios of anti-OVA IgG2a titer to anti-OVA IgG1 titer (IgG2a/IgG1 ratios) and cytokine profiles. Results. Anti-OVA total IgG antibody titer of mice administered OVA in saline was approximately 3.5-fold higher than that of the mice administered OVA in W/O emulsion at a dose of 0.1 mg/mouse/day. Similar total IgG responses were observed between the above two at a dose of 1 mg/mouse/day. The IgG2a/IgG1 ratios decreased as the dose of OVA in W/O emulsion, but not in saline, increased at doses of 0, 0.1, and 1 mg/mouse/day. Interferon- secretion of PLN cells from the mice administered OVA in W/O emulsion decreased, whereas their interleukin-4 secretion remained high. Although interferon- secretion for the mice administered OVA in saline decreased, interleukin-4 secretion did not change. Conclusions. The present study suggests that oral delivery of OVA via the W/O emulsion system may more efficiently enhance the induction of Th2-dominated imbalance than that of OVA in saline.     

康艾注射液对人结直肠癌Lovo细胞Th1/Th2类细胞因子的影响

Objective To explore the effect of Kang'ai injection on Th1/Th2 cytokine in human colon carcinoma cell line Lovo.Methods Lovo cells were cultured by conventional ways until they were in exponential growth phase and then divided into 4 groups:one control group and three experimental groups with different concentration of Kang'ai injection.After 72 hours culture,Th1 type cytokines (IL-2,IFN-γ) and Th2.type cytokines (IL-4,IL-10) in the culture supernatant of Lovo cells in each group were separately detected by double-antibody sandwich enzyme-linked immunosorhent assay (ELISA).Results After the coculture of Lovo cells and Kang'ai injection,Th2 type cytokine levels in the supernatants were significant lower than the control group (P＜0.05),and Th1 type cytokines in each group were of little change.Conclusions Kang'ai injection markedly downregulated Th2 type cytokines in Lovo cells,and contributed to the switching from Th2 to Th1.     

呼吸道合胞病毒(RSV)与Th1/Th2细胞因子的关系研究进展

目的对感染呼吸道合胞病毒产生的Th1、Th2型细胞因子种类及其对Th1/Th2型反应平衡的影响进行综述。方法在查阅国内外文献的基础上,介绍各种细胞因子在呼吸道合胞病毒(RSV)感染中的作用、地位。结果与结论虽然到目前为止各种细胞因子在各实验中得出的结果,甚者是对于RSV感染更倾向于发生Th1型还是Th2型反应仍有争论,但Th1/Th2反应平衡在RSV治疗和开发防治药物方面仍具有重要意义。     

妊娠期高血压疾病患者外周血和蜕膜Th1/Th2失衡的研究

目的研究妊娠期高血压疾病患者外周血和蜕膜组织中CD4 T辅助细胞(Th1)和(Th2)细胞免疫反应的变化,探讨Th1/Th2比率失衡在妊娠期高血压疾病发生中的作用。方法选取住院分娩的子痫前期(PE)患者25例(子痫前期组,包括轻度10例和重度15例),妊娠期高血压患者10例,同期住院分娩的正常孕妇12例和自愿参与实验的年龄匹配的健康未孕妇女12例作为对照组,治疗前抽取各组实验对象空腹肘静脉抗凝血0.5m l送流式检验Thl,Th2细胞百分比及Thl/Th2比率。三组孕妇均于剖宫产术胎盘娩出后,立即搔刮子宫腔取蜕膜制成单细胞悬液,分离离心收集淋巴细胞送流式检验Thl,Th2细胞百分比及Thl/Th2比率。结果①子痫前期组外周血Thl细胞百分比(16.18±3.93)%高于其它各组(P<0.01),PE患者Th1/Th2细胞比率(16.75±3.84)均高于其余各组(P<0.05)。②子痫前期组蜕膜组织中CD4 T细胞中Thl百分比(37.83±12.04)%显著高于其它各组(P<0.001),妊娠期高血压患者蜕膜组织中Thl细胞百分比(16.30±5.36)%也高于正常妊娠妇女(11.79±4.61)%(P<0.05)。PE患者Thl/Th2比率(26.70±9.40)显著高于其余各组(P<0.001),重度PE组(30.11±10.42)高于轻度PE组(21.59±4.25)(P<0.05);妊娠期高血压患者Th1/Th2比率(13.13±5.62)也高于正常妊娠妇女(7.61±4.63)(P<0.05)。结论子痫前期患者体内存在着免疫失衡现象。Thl/Th2细胞平衡向Thl漂移,Th2受抑制可能是妊娠期高血压疾病(包括子痫前期和妊娠期高血压)发生的重要原因。     

Role of NF‐κB activation and Th1/Th2 imbalance in pulmonary toxicity induced by nano NiO

With the progress of nanotechnology, nano nickel oxide (NiO) has been extensively used as sensors, battery electrodes, catalysts, and cosmetics. Previous researches verified that nano NiO could exert pulmonary toxicity, but its mechanism was unclear. To shed light upon this, the role of nuclear factor‐κ B (NF‐κ B) activation and Th1/Th2 imbalance were to explore in pulmonary damage induced by nano NiO. Male Wistar rats were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg kg^?1) and micro NiO group (0.024 mg kg^?1) and treated by intratracheal instillation twice a week for 6 weeks. The results showed that the abnormal changes induced by nano NiO were found on indicators of nitrative stress (NO, TNOS, and iNOS), inflammatory cytokines (TNF‐α , IL‐2, and IL‐10) and cytokine‐induced neutrophil chemoattractants (CINC‐1, CINC‐2αβ , and CINC‐3) in lung tissue. In addition, nano NiO instillation induced the upregulated mRNA and protein expression of NF‐κ B, inhibitor of κB kinase‐α (IKK‐α ) and nuclear factor‐inducing kinase (NIK). The protein content of GATA‐3 increased as well as T‐bet decreased in nano NiO groups, and the ratio of T‐bet/GATA‐3, as a key evaluation indicator of Th1/Th2 balance, was lower than the control group. The findings indicated that nano NiO could enhance the nitrative stress and inflammatory response in lung tissue, and its mechanism was related to the NF‐κ B activation and Th1/Th2 imbalance. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1354–1362, 2017.     

白藜芦醇苷对内毒素休克肺损伤大鼠Th1/Th2失衡的干预作用

目的:探讨白藜芦醇苷对内毒素休克肺损伤大鼠Th1/Th2类细胞因子水平失衡的影响。方法:采用颈静脉注入LPS复制大鼠急性肺损伤模型,ELISA法检测其外周血单个核细胞产生IFN-γ、IL-4水平及IFN-γ/IL-4比值并观察PD对其影响。结果:在体内实验中,PD能使IL-4水平显著升高(P<0.001),使失衡的IFN-γ/IL-4比值接近正常对照组,肺组织病理切片显示肺损伤减轻;在体外实验中,与急性肺损伤对照组比较,IFN-γ、IL-4水平虽无显著差异(P>0.05),但IFN-γ/IL-4比值接近正常对照组(P>0.05)。结论:PD在体内、外实验中,能纠正内毒素休克大鼠体内失衡的Th1/Th2类细胞因子水平,减轻肺损伤。     

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide-coated vanadium oxide nanoparticles to human lung cells

Due to excellent metal–insulator transition property, vanadium dioxide nanoparticles (VO₂ NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO₂ NPs exposure through various routes. Herein, the cytotoxicity of VO₂ NPs (N-VO₂) and titanium dioxide-coated VO₂ NPs (T-VO₂) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO₂ NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO₂ NPs. Under the same conditions, T-VO₂ NPs showed slightly lower cytotoxicity than N-VO₂ in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO₂ NPs. Titanium dioxide coating changed the surface property of VO₂ NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO₂ NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO₂ NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.     

康艾注射液对人结直肠癌Lovo细胞Th1/Th2类细胞因子的影响

目的 探讨康艾注射液对人结直肠癌Lovo细胞Th1/Th2状态的影响.方法 常规培养Lovo细胞,待细胞处于指数增长期再分成4组:1组为空白对照,另外3组加入不同浓度的康艾注射液.培养72h后,采用双抗夹心酶联免疫吸附法(ELISA)分别检测各组Lovo细胞培养上清中Th1类细胞因子(IL-2,IFN-γ)和Th2类细胞因子(IL-4,IL-10)的水平.结果 Lovo细胞与康艾注射液共培养后,上清液中Th2类细胞因子的含量较对照组明显降低(P＜0.05),而Th1类细胞因子在各组中的含量变化不大.结论康艾注射液可显著下调Lovo细胞Th2类细胞因子水平,具有促进其Th2向Th1逆转的倾向.     

1型糖尿病外周血Th1/Th2细胞因子表达水平的研究

目的检测1型糖尿病患者外周血CD_4~+T细胞分泌细胞因子的水平变化,探讨患者Th1/Th2细胞因子的平衡状态及其在1型糖尿病中的作用。方法对49例1型糖尿病患者和30例健康时照组外周血用刺激物刺激细胞,增加细胞内细胞因子的表达,再加入荧光标记的特异性抗细胞因子单克隆抗体,特异性抗原抗体结合,以流式细胞仪分析特异性细胞因子表达水平。结果1型糖尿病患者Th1型细胞因子干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)表达水平较正常对照组升高,差异有统计学意义(P<0.01)。Th2型细胞因子白细胞介素-4(IL-4)、白细胞介素-10(IL-10)表达水平较正常时照组显著降低,差异有统计学意义(P<0.01)。结论1型糖尿病患者Th1/Th2平衡失调,Th1型反应模式处于优势状态,Th2型反应模式处于弱势状态。Th1/ Th2平衡向Th1方向漂移。     

环境真菌链格孢霉对小鼠Th1/Th2平衡及气道反应性的影响

目的 探讨环境真菌链格孢霉（Alt,Alternaria）对小鼠Th1/Th2平衡及气道反应性的影响.方法 通过将小鼠暴露于链格孢霉提取物建立小鼠模型,以鸡卵蛋白（OVA）为阳性对照,探索真菌链格孢霉对Th1/Th2平衡及哮喘特征性指标的影响.结果 与OVA相似,Alt暴露引起了气道炎症细胞总数（P＜0.01）、嗜酸性细胞数增加（P＜0.01）;诱导了气道敏化和Th2反应并引起肺部和支气管的病理学变化.Alt与OVA间存在协同作用.结论 实验结果表明,环境真菌可通过干扰气道Th1/Th2平衡继而导致炎症,最终引起哮喘的发生.     

CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子表达的影响

目的：探讨CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子的调节作用及气道炎症的抑制作用。方法：采用酶联免疫中附法（ELISA）分别检测CpG-ODN对哮喘小鼠抗原首次激发后24小时和抗末次激发后24小时血清及支气管肺泡灌洗液（BALF）中Th2细胞因子IL－4和Th1细胞因子IFNγ水平的影响，并与激素治疗组和哮喘组对照。结果：（1）抗原末次激发后24小时，CpG-ODN 血清及BALF中IFNγ水平高于哮喘组及地塞米松组（P＜0．001）。（2）抗原首次激发后24小时及抗原末次激发后24小时血清和BALF中IL－4水平低于哮喘组（P＜0．05），与地塞米松组比较无显著性差异（P＞0．05）。（3）抗原末次激发后24小时，CpG-ODN组外周血和BALF中嗜酸性粒细胞计数均低于哮喘组（P＜0．001）。结论：CpG-ODN不仅有具有与地塞米松相同的下调Th2细胞因子表达和抑制嗜酸性粒细胞的作用，而且还具有地塞米松所没有的诱导Th1细胞因子表达的作用。说明其可能通过调节Th1/Th2平衡而达到在早期抑制哮喘发病的目的。     

宫颈鳞癌患者Th1/Th2平衡状态的研究

目的 观察宫颈鳞癌患者T细胞亚群的漂移状态.方法 采用ELISA法,对65例宫颈鳞癌患者和40例正常人群的血清中的IL-2、IFN-γ、IL-4、IL-10进行测定.结果 宫颈鳞癌患者血清中IL-2、IFN-γ水平较正常对照组明显降低(P＜0.01),宫颈鳞癌患者血清中IL-4、IL-10高于对照组,统计处理有显著性差异(P＜0.05).结论 宫颈鳞癌患者存在典型的Th2漂移现象,机体免疫抑制,导致肿瘤发生,同时为宫颈鳞癌的生物治疗提供靶点.     

阿奇霉素对哮喘致敏大鼠气道炎症及Th1/Th2失衡的调节作用

目的:探讨阿奇霉素对哮喘(OVA)致敏大鼠气道炎症及Th1/Th2失衡的调节作用.方法:SD大鼠40只,随机分为生理盐水组、哮喘模型组、地塞米松组以及阿奇霉素组,每组10只.利用卵白蛋白(Ovalbumin,OVA)/Al (OH)3 致敏与OVA雾化吸入激发建立大鼠过敏性气道炎症模型,收集肺泡灌洗液(BALF)进行白细胞分类计数.采用ELISA法测定肺泡灌洗液中IL-2、IL-4、TNF-α与ET-1的表达情况.光镜观察肺组织病理结构变化.结果:OVA模型大鼠肺泡灌洗液中的中性粒细胞、淋巴细胞以及嗜酸性粒细胞含量明显增加;HE染色观察肺组织病理结构出现明显的支气管上皮脱落、杯状细胞增生,支气     

Effects of Th1 and Th2 cells balance in pulmonary injury induced by nano titanium dioxide

To explore the potential immunoregulatory mechanisms linking nano TiO₂ and pulmonary injury, Sprague Dawley rats were exposed by intra-tracheal instillation to nano TiO₂ with the individual doses of 0.5, 4.0 and 32 mg/kg b.w., micro TiO₂ with 32 mg/kg b.w. and 0.9% NaCl, respectively. The exposure was conducted twice a week, for four consecutive weeks. The results of lung histology demonstrated increased macrophages accumulation, extensive disruption of alveolar septa, slight alveolar thickness and expansion hyperemia. Mitochondria tumefaction organelles dissolution, endoplasmic reticulum expansion and the gap of nuclear broadening were shown. The changes of IFN-γ and IL-4 level showed no statistical difference. The mRNA expression of GATA-3 was up-regulated, whereas T-bet was significantly down-regulated. The protein expression of T-bet decreased and there were significant differences in nano 4 and 32 mg/kg groups. The imbalance of Th1/Th2 cytokines might be one of the mechanisms of immunotoxicity of respiratory system induced by nano TiO₂ particles.     

变应性鼻炎患者血清Th1/Th2细胞因子水平变化及孟鲁司特的干预作用

目的 探讨变应性鼻炎患者血清Th1/Th2细胞因子水平的变化及孟鲁司特的干预作用.方法 选择变应性鼻炎患者40例（治疗组）予以孟鲁司特片10 mg口服,1次/d,连用8周.观察患者治疗前后外周血中γ-干扰素（IFN-γ）和白介素-4（IL-4）水平的变化,并进行临床疗效及安全性的观察.另选择同期体检的正常健康者30例作为对照组.结果 治疗组患者治疗前培养上清中IFN-γ水平[（8.74±1.37） ng/mL]明显低于对照组[（15.13 ±3.16） ng/mL],IL-4水平[（1.64±0.47）ng/mL]明显高于对照组[（0.72±0.21） ng/mL]（t=2.93、3.52,均P＜0.01）.治疗8周后,患者培养上清中IFN-γ水平[（12.36±2.56） ng/mL]均较治疗前[（8.74±1.37） ng/mL]明显上升,IL-4水平[（1.21±0.28） ng/mL]均较治疗前[（1.64±0.47） ng/mL]明显下降（t=2.36、2.31,均P＜0.05）;且治疗组治疗8周后,临床总有效率92.5％ （37/40）,治疗期间未发生严重的药物不良反应.结论 变应性鼻炎患者存在外周血Th1/Th2细胞因子的失衡.孟鲁司特治疗变应性鼻炎的疗效确切,安全性较好,作用机制与其能降低外周血IL-4水平,提高外周血IFN-γ水平,纠正Th1/Th2细胞因子的平衡紊乱,使免疫反应由Th2型向Th1型转变密切相关.     

1型糖尿病并发血管病变患者Th1/Th2细胞亚群的研究

目的探讨1型糖尿病并发血管病变患者体内Th1/Th2细胞亚群的变化。方法用酶联免疫吸附测定（ELISA）检测了15例1型糖尿病合并有下肢血管病变患者血清中Th1型细胞亚群分泌的细胞因子IFN-γ、TNF-α和Th2型细胞亚群分泌的细胞因子IL-4、IL-10的水平变化,20例无糖尿病早期合并症患者和20例健康志愿者做为对照组。结果1型糖尿病患者血清中Th1型细胞因子IFN-γ、TNF-α的水平显著高于对照组（P〈0.01）;Th2型细胞因子IL-4、IL-10的水平明显低于对照组（P〈0.01）;糖尿病并发血管病组Th1型细胞因子IFN-γ、TNF-α显著高于单纯糖尿病组（P〈0.05）,而Th2型细胞因子IL-4、IL-10的水平明显低于单纯糖尿病组（P〈0.05）。结论当1型糖尿病并发血管病变时,患者体内Th1/Th2细胞亚群发生了Th2-Th1的漂移改变。     

黄芪对儿童变应性鼻炎血清Th1/Th2的影响

目的通过观察黄芪对变应性鼻炎患儿的Th1/Th2细胞因子的影响,探讨黄芪对变应性鼻炎的作用机制。方法60例变应性鼻炎患儿随机分黄芪治疗组和常规治疗对照组。两组均采用常规治疗,治疗组加用黄芪颗粒1/2包(7.5g),3次/d,疗程2￣6个月。观察患儿2个月内总有效率及用药前和用药2个月后血清Th1和Th2基因表达和蛋白产生水平的变化。结果2个月后黄芪治疗组总有效率显著高于常规治疗组,差异有统计学意义(χ2=0.666,P<0.05),用药后黄芪治疗组、常规治疗组血清Th1比例上升显著,高于健康对照组;用药后黄芪治疗组、常规治疗组Th2比例下降显著(P<0.05),而黄芪治疗组显著高于常规治疗组(P<0.05)。结论黄芪能纠正变应性鼻炎患儿体内Th1/Th2细胞因子的失衡状态,提高缓解率。     

原因不明习惯性流产患者细胞免疫状态和Th1／Th2细胞因子的变化

目的 探讨原因不明习惯性流产(URSA)患者T细胞、NK细胞亚群和Th1/Th2细胞因子的变化.方法 用流武细胞仪测定65侧URSA患者和30饲正常妊娠妇女外周血CD3 、CD4 、CD8 、CD16 CD56 细胞亚群比例,同时用ELISA法测定两组外周血Th1/Th2细胞因子的含量.结果 与正常妊娠组相比,URSA患者CD4 、CD4 /CD8 、CD16 CD56 百分比较高,而CD8 较低(P相似文献   

支气管哮喘患儿Th1/Th2细胞免疫平衡变化研究

目的探讨支气管哮喘患儿Th1/Th2细胞免疫平衡变化及其机制。方法选择急性发作期支气管哮喘患儿30名作为发作组,选择30名缓解期支气管哮喘患儿作为缓解组,选择30名健康小儿作为对照组,采用流式细胞仪检测各组静脉血Th1、Th2表达情况,采用酶联免疫吸附法检测三组患儿血清IL-4、IL-10、IFN-γ水平,比较各组患者Th1/Th2及血清IL-4、IL-10、IFN-γ表达变化水平。结果发作组静脉血Th1/Th2低于对照组及缓解组,血清IL-4、IL-10水平高于对照组及缓解组,IFN-γ水平低于对照组及缓解组。缓解组静脉血Th1/Th2低于对照组,血清IL-4、IL-10水平高于对照组,血清IFN-γ水平低于对照组。结论支气管哮喘患儿存在Th1/Th2免疫失衡,其可能是小儿支气管哮喘的发病机制之一。