CCK-8对KLH免疫小鼠脾细胞Th1/Th2平衡的影响

目的： 探讨八肽胆囊收缩素（CCK-8）对Th1/Th2平衡的调节作用。方法: 给予BALB/c小鼠钥孔戚血蓝蛋白（KLH）免疫同时体内给予不同剂量的CCK-8,酶联免疫吸附试验(ELISA)检测其脾细胞培养上清中Th1型细胞因子γ-干扰素(IFN-γ)、白细胞介素-2（IL-2）和Th2型细胞因子白细胞介素-4（IL-4）、白细胞介素-5（IL-5）水平,逆转录聚合酶链式反应(RT-PCR)法检测脾细胞中IFN-γ、IL-2、IL-4、IL-5 mRNA表达;ELISA法检测血清中Th1型抗KLH抗体IgG2a和Th2型抗KLH抗体IgG1水平。结果: ①KLH免疫使小鼠脾细胞分泌Th1/Th2型细胞因子水平明显增高,mRNA表达增高,KLH免疫同时给予CCK-8可使脾细胞培养上清中IFN-γ、IL-2含量进一步增加和IFN-γ、IL-2mRNA表达增高,而使IL-4、IL-5含量降低,IL-4、IL-5 mRNA表达减低和降低IL-4/IFN-γ比值。②KLH免疫小鼠血清中IgG2a、IgG1发生不同程度增高,CCK-8可使其血清中IgG1水平减低而使IgG2a水平增高。结论: CCK-8可促进KLH免疫小鼠体内Th1反应,使Th2优势反应向Th1方向转变。     

血清Th1/Th2细胞因子水平与慢性丙型肝炎临床及干扰素疗效关系的研究

目的 探讨血清Th1和Th2细胞因子水平与慢性丙型肝炎患者病情进展及干扰素疗效的关系.方法 血清细胞因子检测应用ELISA法,HCV基因分型应用直接测序法,HCVRNA载量采用荧光定量PCR法.结果 慢性丙型肝炎患者血清IL-2和TGF-β含量明显低于健康对照组,IL-5含量明显高于后者;血清IL-6含量与ALT水平呈正相关,与RNA载量呈负相关;HCV基因型1型患者IL-6含量明显高于2型,2a型IL-2含量低于2b型;随着感染时间的延长,血清IL-2呈下降趋势,IL-6呈升高趋势,而TGF-β则先升高之后逐渐下降.干扰素治疗应答组和无应答组治疗前血清细胞因子水平均差异无统计学意义,但应答组治疗结束时IFN-γ含量较治疗前明显升高.结论 慢性丙型肝炎患者存在Th1/Th2细胞因子失衡并与临床表现相关;治疗前血清Th1/Th2细胞因子水平不能对疗效进行预测,干扰素诱导的Th1细胞优势反应与持续应答有关.     

接种纯化人用狂犬病疫苗对Th1/Th2类细胞因子谱的影响

目的 研究人用狂犬病纯化疫苗(RV)对人体抗原特异性Th1/Th2细胞因子谱的影响.方法 对20例暴露者进行RV的全程接种,在开始接种RV的第0天、14天、45天时分别采血并分离人外周血单个核细胞(PBMC)与RV进行培养,采用ELISA法检测血清抗狂犬病病毒抗体,体外培养检测淋巴细胞转化增殖能力(MTT法),流式微球分析技术(CBA)法检测细胞培养上清液中Th1类细胞因子(IFN-γ、TNF、IL-2)及Th2类细胞因子(IL4、IL-5、IL-10)的水平.结果 暴露组全程注射RV后,19例于第45天、1例于第60天检测血清抗狂犬病病毒抗体阳性,阳性率100%.RV刺激后,暴露组第14天、第45天淋巴细胞增殖能力显著增高,第45天淋巴细胞增殖能力明显高于第0天(P<0.05);当RV刺激后,暴露组第14天、第45天产生IFN-γ、IL-2、IL-4、IL-5的含量高于未刺激组及暴露组第0天水平(P<0.05);TNF、IL-10的含量各组间比较差异无统计学意义(P>0.05).结论 RV在刺激机体产生体液免疫的同时,可以诱导机体产生特异性细胞免疫,Th1的免疫应答尤为显著,提示细胞免疫在预防和控制狂犬病病毒感染中发挥重要的协同作用.     

CpG ODN对rHBsAg免疫小鼠Th1/Th2型免疫应答的影响

目的：初步探讨CpC寡脱氧核苷酸(CpG ODN)与重组乙型肝炎表面抗原(rHBsAg)联合免疫小鼠的Th1／Th2型免疫应答效应。方法：BALB／c小鼠经后腿胫骨前肌免疫2次，ELISA法检测血清乙型肝炎表面抗体(抗-HBs)IgG亚类IgG2a/IgG1的比值；生物活性法检测脾细胞诱生上清中的IFN-γ和IL-2含量；ABC-ELISA法检测小鼠血清中IL-4、IL-10及IL-12含量。结果：加CpG ODN组与单独注射rHBsAg组相比：抗-HBs IgG亚类IgG2a／IgG1比值明显高；Th1型细胞因子IFN-γ和IL-2的表达增强，抑制Th2型细胞因子IL-4和IL-10的产生。结论：CpCODN能够明显增强rHBsAg免疫小鼠Th1型抗体亚类IgG2a的产生，并且诱导Th1型细胞因子的表达，抑制Th2型细胞因子的表达。     

慢性乙肝、肝硬化和肝癌患者Th1/Th2细胞因子检测及临床应用

目的:应用流式微球技术(cytometric bead array,CBA)技术检测慢性乙肝、肝硬化及肝细胞性肝癌(hepatic cellular cancer,HCC)患者血浆中Th1/Th2细胞因子水平,探讨其临床应用。方法:选择慢性HBV感染者71例,HBV阳性肝硬化患者33例,HBV阳性肝癌患者25例,用CBA方法检测其血清中Th1类细胞因子TNF-α、IFN-γ、IL-2,Th2类细胞因子IL-4、IL-5、IL-10的表达情况。结果:肝癌患者血清中Th1类细胞因子TNF-α、IFN-γ、IL-2,Th2类细胞因子IL-5表达显著高于慢性乙肝和肝硬化患者,而IL-4、IL-10在三组患者中的表达无显著性差异。结论:肝癌患者机体强势分泌Th1类细胞因子,处于高免疫反应状态。检测乙肝患者Th1/Th2类细胞因子对于肝病慢性化的进展成为一项新的临床预测指标。     

特发性血小板减少性紫癜患者Th1/Th2的细胞因子水平及临床意义

目的:检测特发性血小板减少性紫癜(ITP)患者外周血Th1(IL-2、IFN-γ)及Th2(IL-4、IL-10)细胞因子的变化,探讨ITP患者发病与Thl/Th2优势活化状态之间的关系.方法:通过酶联免疫吸附试验(ELISA)法检测30例ITP患者治疗前、治疗后及26例健康志愿者外周血清中IL-2、IFN-γ、IL-4、IL-10水平.结果:ITP患者治疗前IFN-γ及IL-2因子水平高于治疗后和对照组,差异有统计学意义(P＜0.05),而IL-4及IL-10因子治疗前水平低于治疗后和对照组,差异有统计学意义(P＜0.05).结论:Thl型细胞因子介导的免疫应答在ITP的发病机制中占主导地位,糖皮质激素治疗可调整Th1/Th2细胞因子的偏移状态.     

腹泻型肠易激综合征患者外周血Th1/Th2细胞因子失衡表达的分析

目的:分析腹泻型肠易激综合征(IBS)患者外周血Th1/Th2细胞因子失衡表达。方法:连续选择近期就诊的腹泻型IBS患者27例,对照组为31例同龄、同性别的同期健康体检者。两组对象接受了外周血Th相关细胞因子γ-干扰素(IFN-γ)、白细胞介素-4(IL-4)检测,并计算IFN-γ/IL-4比值。结果:腹泻型IBS组外周血IFN-γ浓度及IFN-γ/IL-4比值均明显高于对照组,而血清IL-4浓度则显著低于后者(P均<0.05～0.01)。结论:腹泻型IBS患者存在明确Th1优势失衡表达。     

Th1/Th2细胞因子结合甲状腺自身抗体检测在自身免疫性甲状腺疾病中的诊断价值

研究Th1/Th2细胞因子和甲状腺自身抗体在自身免疫性甲状腺疾病(AITD)中的诊断价值。选择Graves病(GD)28例、甲亢甲炎(GDIII)15例、桥本甲亢(HTL)13例、桥本甲状腺炎(HT)21例、20名正常人,通过酶免法检测血清Th1型细胞因子γ干扰素(IFN-γ)和Th2型细胞因子白细胞介素-4(IL-4)的含量,与放免法测定的促甲状腺激素受体抗体(TRAb)、甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)进行相关分析。结果显示,IFN-γ水平HT>HTL>GDIII>GD,IL-4水平GD>GDIII>HTL>HT。GDIII和HTL组IFN-γ和IL-4水平均有统计学意义(P<0.05,P<0.01),GDIII和HTL组TGAb、TPOAb无统计学意义(P>0.05)。HT组IFN-γ与TGAb、TPOAb正相关(r分别为0.67,0.54,P<0.01),GD组IL-4与TRAb正相关(r=0.71,P<0.01)。Th1/Th2细胞因子失衡反映了AITD的病理改变和免疫功能紊乱,与甲状腺自身抗体检测相结合可成为AITD辅助诊断的指标。     

米非司酮通过增强母-胎界面Th1型偏移导致流产

目的：探讨米非司酮对母胎界面Th1/Th2型细胞因子动态平衡的影响.方法：将63例早孕期妇女随机分为2组,一组一次服用米非司酮200 mg,另一组为对照组,收集其蜕膜组织.应用免疫组化法,评价Th1型细胞因子（IL-2、IFN-γ）、Th2型细胞因子（TGF-β2、IL-4）的表达.结果：正常妊娠时,在母-胎界面Th2型细胞因子（IL-4）以及TGF-β2的表达较高;Th1型细胞因子（IL-2、IFN-γ）的表达较低,尤其是IL-2.服用米非司酮后,蜕膜Th1型细胞因子（IL-2、IFN-γ）表达显著升高;而母-胎界面Th2型细胞因子（IL-4）以及TGF-β2的表达无明显变化.结论：米非司酮打破了正常妊娠时母胎界面Th2型免疫优势;显著升高Th1型细胞因子（IL-2、IFN-γ）表达,形成了Th1型免疫偏离,导致流产的发生.     

急性MCMV感染对小鼠脾Th1/Th2/Th17细胞亚群分化的影响

目的:在整体水平观察小鼠巨细胞病毒(MCMV)感染对小鼠脾Th1/Th2/Th17细胞亚群分化及其主要的效应性细胞因子(IFN-γ、IL-4、IL-17A)表达的影响.方法:建立MCMV感染模型,8只BALB/c小鼠分别于接种MCMV Smith株后3天和14天各处死4只;另设8只接种唾液腺匀浆的模拟感染小鼠作为对照.用空斑形成试验测定肝、脾和唾液腺组织病毒滴度;流式细胞术检测脾T淋巴细胞中Th1(CD4+ IFN-γ+)、Th2(CD4+ IL-4+)、Th17(CD4+IL-17A+)细胞比例,双抗体夹心ELISA法检测脾细胞培养上清中病毒特异性IFN-γ、IL-4、IL-17A水平.结果:MCMV感染早期肝、脾和唾液腺组织中病毒呈低水平复制,而感染后14天仅在唾液腺组织呈高水平复制;Th1细胞比例及病毒特异性IFN-γ主要在MCMV感染早期呈显著升高(P ＜0.01);Th2细胞及IL-4均无明显表达及改变;Th17细胞及病毒特异性IL-17A则主要在感染后14天升高(P＜0.05).结论:MCMV感染早期,机体通过上调Th1细胞分化比例及IFN-γ的表达发挥抗病毒效应,而MCMV诱导Th17细胞分化及IL-17A的高表达可能是MCMV感染致宿主特异性细胞免疫功能失调并逃避机体特异性细胞免疫攻击的原因之一.     

Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children

BACKGROUND: Allergic diseases are believed to be due to T helper (Th)2-like immunity to allergens in affected tissues, and immune responses to allergens are characterized by a cross-regulation between Th1 and Th2 cells. Atopic individuals may develop IgE antibodies to only one or more allergens. However, the mechanisms behind sensitization to a specific allergen, e.g. why an individual develops IgE to cat but not birch, are not known. Our aim was to study birch- and cat-induced Th1 and Th2 cytokine secretion in children who were sensitized to birch but not to cat, and vice versa. MATERIALS AND METHODS: The subjects in the study were 60 12-year-old children. Seventeen of the children were sensitized (skin prick test and circulating IgE positive) to birch but not cat, 13 were sensitized to cat but not birch, 11 were sensitized both to birch and cat, and 19 children were skin prick test and circulating IgE negative. Forty-six children had a history of atopic symptoms, and 42 of them had current symptoms. Peripheral blood mononuclear cells were separated from venous blood and stimulated with cat or birch allergen. The levels of IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma in the cell supernatants were analysed by ELISA. RESULTS: Sensitized children produced more of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 than non-sensitized atopic and non-atopic children in response to stimulation with the allergen they were sensitized to. High levels of the Th2 cytokines IL-4 and IL-5 and low levels of the anti-inflammatory cytokine IL-10 were associated with atopic symptoms, and high cat-induced IL-9 levels with asthma. CONCLUSIONS: The Th2 cytokines IL-4, IL-5, IL-9 and IL-13 were all commonly detected in sensitized children after stimulation with the specific, in contrast to an unrelated, allergen. Atopic symptoms were associated with increased levels of IL-4 and IL-5 and tended to be associated with low levels of IL-10, and asthma with high cat-induced IL-9 levels.     

白三烯受体拮抗剂对呼吸道合胞病毒肺炎血清Th1/Th2细胞因子水平影响的研究

目的探讨白三烯受体拮抗剂对呼吸道合胞病毒肺炎患儿血清中Th1／Th2细胞因子、半胱氨酰白三烯水平的影响，研究降低呼吸道合胞病毒肺炎发展为哮喘的有效干预途径。方法将37例呼吸道合胞病毒肺炎患儿分为白三烯受体拮抗剂干预组：顺尔宁，4mg qd，疗程12周，糖皮质激素吸入干预组：出院后给予糖皮质激素吸入，200μg qd／bid，疗程12周。两组患儿入院后24h内及疗程结束用酶联免疫法检测CysLTs、IFN-γ、IL-4。另选10例健康同龄儿童血清标本作对照。结果呼吸道合胞病毒肺炎患儿血清中Th1／Th2细胞因子表达存在失衡，血清CysLTs水平明显高于健康对照组（t=7．85，P〈0．05）；顺尔宁干预组和糖皮质激素吸入干预组均能纠正Th1／Th2细胞因子失衡，差异无统计学意义（P〉0．05）。糖皮质激素吸入干预组血清CysLTs水平治疗前后无明显变化，差异无统计学意义（P〉0．05），顺尔宁干预组血清Cys仉水平治疗后明显下降，差异有统计学意义（P〈0．05）。结论呼吸道合胞病毒肺炎患儿存在Th1／Th2细胞因子失衡、血清CysLTs水平较健康同龄儿童明显升高，与哮喘有相似之处。白三烯受体拮抗剂早期干预能纠正Th1／Th2细胞因子失衡，降低血清CysLTs水平。     

支气管哮喘患儿治疗前后外周血Th1／Th2相关细胞因子的临床分析

目的：探讨支气管哮喘患儿治疗前后外周血Th1／Th2相关细胞因子水平的变化及临床意义。方法i应用放射免疫分析和酶联法对31例支气管哮喘患儿进行了外周血中Th1型细胞因子（IL-2、IFN-1）和Th2型细胞因子IL-4、IL-10浓度,并与35名正常人组作比较。结果i支气管哮喘患儿在治疗前血清IL-2、IFN-^y水平均非常显著地低于正常儿组（P〈0．01）,而血清IL4、IL-10水平又非常显著地高于正常儿组（P〈0．01）。经治疗1个月后则与正常儿组比较无显著性差异（P〉0．05）。结论：支气管哮喘患儿存在Th1／Th2细胞免疫失衡。Th1免疫功能低下。IFN-1下调可能是参与哮喘发病机制的重要原因,对哮喘有负向调节作用。哮喘患儿存在Th2细胞免疫功能亢进,以IL-4、IL-10为代表的Th2免疫功能在儿童哮喘的发病中发挥正性促炎作用。     

Gene–gene interaction between interleukin-4 and interleukin-4 receptor α in Korean children with asthma

BACKGROUND: Interleukin-4 receptor alpha (IL-4Ralpha), which binds IL-4 and IL-13, is involved in signal transduction of those cytokines that lead to IgE production, and is also a key functional component of the Th2 lymphocyte phenotype. OBJECTIVE: To determine whether IL-4 and IL-4Ralpha polymorphisms are associated with susceptibility to asthma and whether there are gene-gene interactions between IL-4 and IL-4Ralpha polymorphisms. METHODS: We genotyped three groups of Korean children, consisting of 196 atopic asthmatics, 60 non-atopic asthmatics, and 100 healthy children, for an IL-4 promoter polymorphism (C-590T) and three IL-4Ralpha polymorphisms (Ile50Val, Pro478Ser, and Arg551Gln) using PCR-RFLP (restriction fragment length polymorphism) assays. RESULTS: The allele frequencies of the IL-4 (C/T) polymorphism and the Ile50Val and Pro478Ser polymorphisms of IL-4Ralpha did not differ statistically among the three groups of children. For the Arg551Gln polymorphism, the combined genotype frequency of the Arg/Gln heterozygote and the Arg/Arg homozygote was significantly higher in atopic asthmatics (27.6%) than in healthy children (16.0%) (odds ratio (OR) = 1.97, 95% CI (confidence interval) = 1.07-3.71). The eosinophil fraction (%) and bronchial responsiveness were higher in children with the Arg/Gln and Arg/Arg genotype than in those with the Gln/Gln genotype (P = 0.036 and 0.024, respectively). In asthmatic children, combinations of the IL-4 CT/TT genotype and the IL-4Ralpha Arg/Gln and Arg/Arg genotypes were associated with significantly increased risk for development of asthma (OR = 3.70, 95% CI = 1.07-12.78, P = 0.038). CONCLUSIONS: In Korean children, the IL-4Ralpha Arg551 allele may play a role in susceptibility to atopic asthma and correlate with markers of asthma pathogenesis, including increased eosinophil fraction and enhanced bronchial hyper-responsiveness. In addition, a significant gene-gene interaction between the IL-4-590C and the IL-4Ralpha Arg551 allele significantly increases an individual's susceptibility to asthma.     

Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma

Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon-gamma (IFN-gamma) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228.35 versus 138.72 pg/ml, P < 0.001; IL-12: 0.00 versus 0.00 pg/ml, P = 0.001; IL-10: 2.51 versus 0.05 pg/ml, P < 0.034; IL-13: 119.38 versus 17.89 pg/ml, P < 0.001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22.40 versus 11.86 pg/ml and 3.42 versus 0.61 pg/ml, respectively), although the differences were not statistically significant (P = 0.077 and 0.053, respectively). The percentage of IFN-gamma-producing Th cells was significantly higher in normal control subjects than asthmatic patients (23.46 versus 5.72%, P < 0.001) but the percentage of IL-4 producing Th cells did not differ (0.72 versus 0.79%, P > 0.05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29.6 versus 8.38%, P < 0.001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma.     

Cellular immune response of asthmatic children in the presence of anti-Ascaris antibody

The presence of anti-Ascaris (anti-Asc) immunoglobin isotypes alters the risk of allergic asthma. In this study, we analyzed the relationships between serum levels of anti-Asc IgE, IgG1, and IgG4, without concurrent infection by the parasite, and the presence of asthma. We measured cytokine levels from Th1, Th2, and Th17 profiles. Children aged 2–14 years old, asthmatics (n = 64), and non-asthmatics (n = 40) were selected according to the International Study of Asthma and Allergies in Childhood criteria. Asthmatic patients who had positive skin allergy tests were considered to have allergic asthma. Stool exams were performed to exclude children who were parasitized by helminths/protozoans and blood samples were collected in non-parasitized individuals. We performed peripheral blood leukocyte counts and in vitro culture following mitogenic stimulation. Levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17) in the supernatants were measured using a cytometric bead array. Titration of serum total IgE and IgE specific to Ascaris were obtained using ImmunoCAP; IgG1 and IgG4 titers were measured using enzyme-linked immunosorbent assays. Anti-Asc IgE was associated with a higher risk of asthma and an increase in the number of eosinophils and neutrophils. By contrast, anti-Asc IgG1 could be considered a protective factor against asthma, associated with lower levels of circulating neutrophils. There were high levels of IL-6 and TNF-α in asthmatics. Levels of IL-6, but not TNF-α, depended on the presence of anti-Asc IgG1 in serum. Anti-Asc IgE appears to increase risk of asthma, and anti-Asc IgG1 appears to favor decreased neutrophil counts and increased IL-6 levels.     

Th1 and Th2 cytokine levels in nasopharyngeal aspirates from children with human bocavirus bronchiolitis.

BACKGROUND: Human bocavirus (hBoV) is regarded as one of the possible etiologic agents in lower respiratory tract infection and bronchial asthma exacerbation in children despite frequent co-detection with other respiratory viruses. The immunologic response in children with hBoV infection is still not clear. OBJECTIVES: To investigate the profiles of T helper-1 (Th1)/T helper-2 (Th2) cytokines in children with hBoV-associated bronchiolitis. STUDY DESIGN: This study utilized of 59 nasopharyngeal aspirates from 59 infants aged 24 months or younger, including 29 from children with hBoV-related bronchiolitis and 30 with respiratory syncytial virus (RSV)-related bronchiolitis. Eighteen infants hospitalized for elective surgeries were included as controls. Nasopharyngeal aspirates were tested simultaneously for cytokines interleukin (IL)-2, IL-4, IL-5, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha using the Cytometric Bead Array. RESULTS: Significantly higher concentrations of IFN-gamma (p=0.0001), IL-2 (0.006), and IL-4 (p=0.0002) were observed in hBoV positive specimens than in controls. The concentration of IL-10 (p=0.04) and TNF-alpha (p=0.006) in the RSV-positive group was significantly higher than in the hBoV-positive group, while there was no difference in other cytokines concentration between the two groups. CONCLUSIONS: These results showed that both of Th1 and Th2 cytokines were increased in children with hBoV-related bronchiolitis compared to normal controls, but Th2-polarized responses were not observed.     

Interleukin-16 aggravates ovalbumin-induced allergic inflammation by enhancing Th2 and Th17 cytokine production in a mouse model

Asthma is a chronic inflammatory disease that involves a variety of cytokines and cells. Interleukin-16 (IL-16) is highly expressed during allergic airway inflammation and is involved in its development. However, its specific mechanism of action remains unclear. In the present study, we used an animal model of ovalbumin (OVA)-induced allergic asthma with mice harboring an IL-16 gene deletion to investigate the role of this cytokine in asthma, in addition to its underlying mechanism. Increased IL-16 expression was observed during OVA-induced asthma in C57BL/6J mice. However, when OVA was used to induce asthma in IL-16^−/− mice, a diminished inflammatory reaction, decreased bronchoalveolar lavage fluid (BALF) eosinophil numbers, and the suppression of OVA-specific IgE levels in the serum and BALF were observed. The results also demonstrated decreased levels of T helper type 2 (Th2) and Th17 cytokines upon OVA-induced asthma in IL-16^−/− mice. Hence, we confirmed that IL-16 enhances the lung allergic inflammatory response and suggest a mechanism possibly associated with the up-regulation of IgE and the promotion of Th2 and Th17 cytokine production. This work explored the mechanism underlying the regulation of IL-16 in asthma and provides a new target for the clinical treatment of asthma.     

转录因子T-bet/GATA-3比率评价哮喘患者Th1/Th2失衡及CpG ODN干预机制的研究

目的: 探讨哮喘患者PBMCs中转录因子T-bet/GATA-3比率与Th1/Th2细胞失衡的关系及体外CpG干预后T-bet/GATA3比率的变化及其对Th1/Th2细胞平衡的调节作用。方法: 用RT-PCR法测定30例发作期哮喘患者（哮喘组）及20例慢性阻塞性肺病患者（COPD组）及20例正常人（对照组） PBMCs中T-bet mRNA、GATA-3 mRNA及TLR9 mRNA的表达强度，用ELISA法测定血浆IL-4、IL-5、IL-13和IFNγ的表达水平，以观察哮喘患者PBMCs中转录因子T-bet/GATA-3比率与Th1/Th2细胞失衡的关系。将20例发作期哮喘患者的PBMCs分为2部分，一份加入CpG ODN和PHA（CpG组），一份仅加入PHA（对照组），培养48 h后分别收集培养液和细胞，采用RT-PCR法测定细胞中T-bet mRNA、GATA-3 mRNA及TLR9 mRNA的表达强度，ELISA法测定培养液中IL-4、IL-5、IL-13和IFN-γ的表达水平。结果： 哮喘患者PBMCs中T-bet/GATA-3的比率显著低于COPD患者和正常人，IL-4、IL-5、IL-13的水平显著高于COPD患者和正常人，与T-bet/GATA-3的比率呈负相关，而IFN-γ的水平显著降低，与T-bet/GATA-3的比率呈正相关。哮喘组TLR9的表达强度显著弱于COPD患者和正常人。CpG干预组细胞培养液中IL-4、IL-5和IL-13的水平分别显著低于对照组，IFN-γ的水平显著高于对照组。CpG干预组细胞中T-bet mRNA和TLR9 mRNA的表达强度显著强于对照组，GATA-3 mRNA的表达强度显著低于对照组；T-bet/GATA-3的比率显著高于对照组。结论: 哮喘患者T-bet/GATA-3的比率降低，可以作为评价Th1/Th2细胞失衡的精确指标。CpG ODN可以上调T-bet的表达，下调GATA-3的表达，从而上调T-bet/GATA-3的比率，逆转Th1/Th2细胞失衡，是一种很有前景的哮喘治疗手段。     

Assessment of Th1 and Th2 cytokine modulatory activity of an edible fern,Diplazium esculentum

The present study was conducted to determine the effect of Diplazium esculentum on Th1 and Th2 cytokine modulation in Swiss albino mice that were administered orally with different doses of boiled D. esculentum (BDE), daily within a span of 180 days. After the treatment, serum was collected. Splenocytes were also cultured in vitro with different concentrations of BDE, and culture supernatant was collected. Both serum and culture supernatant were used for cytokine determination by enzyme-linked immunosorbent assay (ELISA) for different Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. Results indicated significant decreases (p < 0.05, p < 0.01, and p < 0.001) in both Th1 and Th2 cytokine concentrations when compared with their respective controls. These results suggest that the intake of D. esculentum, even after cooking, may evoke immune dysfunction by altering Th1 and Th2 cytokine balance, may induce severe immunosuppression, and may be considered as alarming.