Early alteration in leukocyte populations and Th1/Th2 function in ethanol-consuming mice

BACKGROUND: Chronic alcohol consumption polarizes the immune response away from Th1-mediated cell-mediated immunity. In the present report we investigate the first onset of alteration in immune parameters during ethanol consumption in terms of changes in splenic leukocyte cellularity and surface phenotype as well as alterations in Th1 and Th2 function. METHODS: BALB/c and C57BL/6 mice were fed ethanol-containing liquid diets, were pair-fed an isocaloric liquid control diet, or were fed solid diet and water ad libitum for up to 12 days. At intervals during the feeding period, splenic leukocytes were assessed for phenotypic markers by flow cytometry and for their ability to support antigen-induced interferon-gamma (IFNgamma) production in a coculture system. Mice were bled at intervals throughout the feeding period, and serum immunoglobin E (IgE) and alcohol levels were determined. RESULTS: Data show that phenotypic and functional alterations occur within the first few days of alcohol consumption. Both liquid diets affect splenic cellularity, and by dietary day 5, ethanol-containing liquid diets further reduce B and NK cell numbers. The decline in B cells is accompanied by a concomitant decline in the amount of major histocompatibility complex class II expressed on this population. Functional alteration in Th1-mediated IFNgamma production occurred in the population fed ethanol-containing liquid diets by dietary day 5. Th2 function, as indicated by systemic serum IgE levels in these unimmunized mice, is increased by dietary day 6 to 8 and correlated with significant blood alcohol levels. CONCLUSIONS: Ethanol consumption by mice causes a rapid decrease in splenic cellularity accompanied by a decrease in Th1 function and a rapid increase in systemic IgE levels.     

SCP提取物合剂对血吸虫卵肉芽肿诱导的Th1型和Th2型细胞因子的调节效应

目的　进一步研究SCP提取物合剂对感染小鼠诱导的抗肝内血吸虫卵肉芽肿病变的调节效应和分子机制。方法　BALB/c小鼠 40只 ,均分为 4组 ,每鼠感染 30± 2条尾蚴。 4w后组I和组III小鼠分别口服SCP提取物SCP1和SCP2 ,并联用“42 5”制剂 14d ,SCP1和SCP2的总量均为 70 0 0 μg ,“42 5”制剂 70 0mg ,组II单用SCP1,用量同上。组IV为对照。停药后1w ,剖检小鼠 ,计算各组小鼠每g肝组织虫卵数 (EPG)和成熟虫卵减少率 ;制成肝组织石蜡切片 ,计算肉芽肿大小 ;分离脾淋巴细胞 ,于 37℃ ,5 %CO2 中培养 48～ 72h ,取上清液 ,测定IFN -γ和IL - 4含量水平 (pg/ml)。 结果　实验组小鼠的EPG均显著低于感染对照鼠者 ,成熟虫卵减少率为 80 .5 6 %～ 87.70 % ;实验鼠肉芽肿的平均面积和体积均显著小于感染对照鼠者 (P<0 .0 5 ) ;实验鼠脾淋巴细胞上清中IFN -γ和IL - 4含量水平均显著低于感染对照鼠的 5 46 .15± 2 43.15和 73.78± 2 8.37。结论应用中药SCP提取物合剂能诱导明显的抗肝内血吸虫卵肉芽肿病变效应及血吸虫性纤维化作用 ,其分子机制与Th1型和Th2型细胞因子应答的调节效应密切相关     

布地奈德雾化吸入对轻中度支气管哮喘患者Th1/Th2细胞因子平衡的影响

目的探讨雾化吸入布地奈德对轻中度支气管哮喘患者Th1/Th2细胞因子平衡的影响。方法49例轻中度支气管哮喘患者随机分为对照组(25例)和治疗组(24例)。两组均予吸氧、抗感染、静脉氨茶碱及对症治疗等。治疗组加用布地奈德混悬液氧气雾化吸入。分别采用ELISA法检测两组哮喘患者治疗前、治疗两周后及健康体检者外周血浆白细胞介素-5(inter-leuk in-5)和IL-12水平;同时测定两组哮喘患者治疗前后的FEV1。结果两组哮喘患者治疗前后血浆IL-5水平明显高于健康体检组,而IL-12水平则明显低于健康体检组,均P0.05;治疗后两哮喘组IL-5、IL-12水平与治疗前比较,均P0.01,治疗组与对照组治疗后比较IL-5、IL-12亦均差异显著;无论是治疗前还是治疗后,两组哮喘患者血浆IL-5与IL-12均呈明显的直线副相关。结论Th1/Th2的失衡与哮喘发病密切相关;布地奈德雾化吸入可通过调节Th1/Th2的平衡而治疗哮喘。     

布地奈德雾化吸入对支气管哮喘患者Th1、Th2型细胞因子的影响

目的探讨布地奈德雾化吸入治疗对支气管哮喘患者Th1、Th2型细胞因子的影响。方法轻、中度支气管哮喘患者共59例,健康对照者10例,检测肺功能,并采哮喘组治疗前及布地奈德雾化吸入治疗后2周的晨起静脉血,与健康对照者比较,检测血中Th1型细胞因子IFN-γ及及Th2型细胞因子IL-5的水平。结果轻、中度哮喘患者体内IFN-γ水平低于健康对照者(P0.05),IL-5水平高于健康对照者(P0.05),经布地奈德治疗后,IFN-γ水平较前增高,IL-5水平较前下降。结论哮喘患者体内Th1型细胞因子IFN-γ的分泌减少,Th2型细胞因子IL-5的分泌增多,布地奈德吸入治疗可在一定程度上提高IFN-γ的水平,降低IL-5的水平,值得关注。     

Immunomodulatory effect of Hypoderma lineatum antigens: in vitro effect on bovine lymphocyte proliferation and cytokine production

This study examines the immunomodulatory effect of a crude larval extract (CLE), obtained from first stage larvae (L1) of H. lineatum , and the purified fractions hypodermin A (HyA), HyB and HyC. Proliferative responses of peripheral blood mononuclear cells (PBMC) from uninfested and previously infested cattle and the production of the cytokines IL-10, IL-4 and IFN-γ, in response to concanavalin A (Con A), were determined. The stimulation index of peripheral blood mononuclear cells from uninfested cattle was significantly lower than that from infested animals with the different antigens assayed. The HyA was the antigen that most inhibited the proliferative response, followed by the HyB, the HyC and the CLE. This hypodermin provoked an increase of IFN-γ and a suppression of IL-10 production that would support a Th1-like cytokine response. The HyB reduced the production of IL-10 stimulated by the Con A in cultures from infested animals. The HyC did not modulate the production of cytokines. Finally, the CLE induced a marked suppression in the production of the different cytokines in cultures from naïve and previously sensitized animals. Our results indicate that Hypoderma larval secretions are comprised of different components (hypodermins) that individually induce distinct but partially overlapping modulatory responses.     

康艾注射液对代偿期肝硬化患者Th1/Th2及相关细胞因子的影响

目的研究康艾注射液对代偿期肝硬化患者Th1/Th2细胞及相关细胞因子的影响。方法采用流式细胞仪检测康艾注射液治疗代偿期肝硬化患者治疗前、后血清Th1、Th2细胞的变化,用ELISA法检测两组患者治疗前、后血清IFN-γ、IL-10的变化。结果两组治疗前后血清Th1、Th2细胞均明显高于健康对照组(P<0.01),Th1/Th2比值均明显低于健康对照组(P<0.01)。治疗后两组Th1、Th2细胞均较治疗前明显下降(P<0.01),Th1/Th2比值均较治疗前明显上升(P<0.01),治疗组Th1/Th2比值明显高于对照组(P<0.01)。两组患者IL-10治疗后明显下降(P<0.01),治疗组低于对照组(P<0.05);两组患者IFN-γ治疗后明显上升(P<0.01),治疗组高于对照组(P<0.01)。结论康艾注射液可以促使代偿期肝硬化患者Th1/Th2平衡向Th1优势漂移,从而促进炎症吸收,促进病情尽早康复。     

Th1和Th2型细胞因子对小鼠感染血吸虫的免疫保护性研究

目的 探讨Th1和Th2类细胞因子对小鼠感染血吸虫的免疫保护作用. 方法 C57BL/6小鼠48只,抽签法随机均分为4组,白细胞介素（interleukin,IL）-4组,给予IL-4 （200 ng）; IL-12组,给予IL-12 （200 ng）;胸腺基质淋巴生成素（thymic stromal lymphopoietin,TSLP）组,给予TSLP（200 ng）;生理盐水组,给予生理盐水（200μl）.4组均为腹腔注射,每周3次,持续注射8周.给药后2周,各组小鼠经皮攻击感染日本血吸虫尾蚴（40±2）条/鼠,感染后第3、6周剖杀,计算各组小鼠虫荷数、肝脏卵荷数.芯片检测各组小鼠感染前和感染后不同时间点血清中IL-5、IL-10、γ-干扰素（interferon-γ,IFN-γ）及肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）的动态变化.观察小鼠肝、脾的病理变化. 结果 细胞因子注射的第8周,IL-4组的Th2类细因子IL-5、IL-10依次为161.97、65.47 μg/ml; TSLP组的IL-5、IL-10依次为132.72、77.18 μg/ml; IL-12组的IL-5、IL-10依次为87.15、12.29 μg/ml;生理盐水组的IL-5、IL-10依次为188.92、167.52 μg/ml.IL-4和TSLP组Th2类细胞因子水平均高于IL-12组,但低于生理盐水组.IL-12组IFN-γ、TNF-α依次为165.7、23.64 μg/ml,水平高于其它各组.感染后3周IL-4、IL-12、TSLP、生理盐水组虫荷数依次为（9.50±4.51）、（12.83±2.32）、（6.75±2.87）、（9.80±3.03）条;感染后6周上述各组虫荷数依次为（18.83±5.91）、（24.80±9.42）、（21.67±3.67）、（17.67±6.74）条,每克肝组织虫卵数依次为（58 286.98±25 351.60）、（80 460.18±35 542.66）、（54 579.56±16 399.21）、（41 094.92±25 598.27）.与生理盐水组相比,各实验组虫荷数与每克肝组织虫卵数差异均无统计学意义.感染后第3周,IL-4、IL-12、TSLP、生理盐水组脾指数依次为（0.010±0.002）、（0.011±0.002）、（0.009±0.001）、（0.007 ±0.001）,各实验组与生理盐水组相比,差异均有统计学意义（t=3.158、5.076、6.204,P＜0.05）.感染后第6?     

不稳定性心绞痛患者体内辅助性T细胞细胞因子变化及意义

目的通过检测不稳定性心绞痛(UAP)患者血清中1型辅助性T细胞(Th1)和2型辅助性T细胞(Th2)细胞因子的变化,探讨其在UAP发病过程中的作用及对近期预后的判断价值。方法选取UAP患者42例(UAP组),稳定性心绞痛(SAP)患者34例(SAP组),同时选取健康体检者22例(对照组)。测定各组血清中的γ-干扰素(IFN-γ)、白细胞介素(IL)-2、IL-4和IL-10水平,并观察UAP患者3个月内不良心脏事件发生率。Th1细胞因子包括IFN-γ、IL-2,Th2细胞因子包括IL-4、IL-10。结果 UAP组血清中IFN-γ、IL-2水平明显高于对照组和SAP组,而IL-4、IL-10水平明显低于对照组和SAP组(P0.05)。UAP患者中,有心脏事件患者血清IFN-γ、IL-2水平明显高于无心脏事件患者,IL-10、IL-4水平明显低于无心脏事件患者(P0.05)。结论外周血中Th1和Th2细胞因子水平变化可能与冠状动脉病变不稳定性斑块的存在有关,可反应冠心病患者临床病情,对判断UAP患者近期预后有较好的预测价值。     

Anti-interleukin-4 treatment diminishes secretion of Th2 cytokines and inhibits hepatic fibrosis in murine schistosomiasis japonica

Anti-interleukin-4 (IL-4) treatment o/"Schistosoma japo-nicum-infected mice markedly inhibited in vitro secretion of the Th2 cytokines IL-4 and IL-5 from antigen-stimulated spleen cells, but enhanced the secretion of the Th1 cytokine IFN-γ. IL-2 secretion was unaffected. Hepatic fibrosis was markedly diminished in anti-IL-4-treated-mice at ten weeks of infection while granulomas around S. japonicum eggs in the livers were slightly-to-moderately increased in size. The number of eggs per worm pair in the tissues and feces did not differ significantly in treated and untreated mice. These findings suggest that Th2 cytokine responses are important in the genesis of schistosomal hepatic fibrosis.     

微卡对致敏小鼠气道炎症和Th1/Th2比例变化的影响

目的　观察母牛分支杆菌菌苗 (微卡 )对致敏小鼠抗原攻击后气道炎症、Th1和Th2细胞因子的比例变化 ,评估微卡防治哮喘的药理作用。方法　小鼠分 9组 ,每组 7～ 1 0只。采用皮肤划痕、气管滴入、肌肉注射三种给药途径单次给药 ,观察比较微卡菌苗对致敏小鼠吸入抗原后支气管肺泡灌洗液 (BALF)中炎症细胞 ,γ干扰素 (IFN γ)和白细胞介素 4(IL 4)水平变化的影响和作用强度。结果　经皮肤划痕 (2 .2 5μg)、气管内滴入 (2 .2 5μg)、肌肉注射 (2 2 .5μg)后BALF中炎症细胞总数分别为 (6± 6)× 1 0 8/L、(7± 6)× 1 0 8/L、(8± 5)× 1 0 8/ml,与模型组 (1 5± 8)× 1 0 8/L比较 (P <0 .0 5) ;嗜酸细胞 :皮肤划痕组 (2 2 5μg)为 0 7± 0 5、气管内滴入 (2 2 5μg)为 1 6± 1 9、肌肉注射 (7 5μg)为 2 6±1 3、肌肉注射组 (2 2 .5μg)为 1 .40± 1 .2 0 ,与模型组 (4.90± 4 .60 )比较 (P <0 .0 5或 <0 .0 1 ) ;皮肤划痕组 (2 .2 5μg)BALF中IFN γ水平为 (2 89± 57)pg/ml、气管滴入组 (2 .2 5μg)为 (335± 57)pg/ml、肌肉注射组 (2 2 .5μg)为 (31 3± 49)pg/ml,与模型组 (2 1 6± 42 )pg/ml比较 (P <0 .0 5或 0 .0 1 ) ;皮肤划痕组(2 .2 5μg) BALF中IL 4水平为 (63± 1 9)pg/ml、气管滴入组     

Massive liver necrosis after provocation of imbalance between Th1 and Th2 immune reactions in osteopontin transgenic mice

Background Massive liver necrosis can develop as a consequence of imbalance between T-helper (Th)1 and Th2 immune reactions in the liver. Osteopontin is a glycoprotein secreted for the initiation of the Th1 immune reaction, as well as for extracellular matrix formation and calcium deposition in the bone and kidney. Osteopontin is overexpressed in Kupffer cells, macrophages, and stellate cells activated in injured livers. We established transgenic mice expressing osteopontin exclusively in hepatocytes, using a vector containing human serum amyloid P component promoter. The relation of Th1/Th2 immune imbalance to massive liver necrosis was studied using these transgenic mice.Methods Transgenic mice and C27BL/6 mice, wild-type controls of the transgenic mice, were given an intravenous injection of concanavalin-A, and the histological extent of liver injuries and plasma cytokine levels were evaluated.Results When the transgenic mice received concanavalin-A, massive necrosis and mononuclear cell infiltration developed in the liver, the extent of which was greater in the female mice than in the male mice. This treatment produced minimal liver injury and focal liver necrosis in male and female C57BL/6 mice. In these transgenic and control mice, plasma concentrations of interleukin (IL)-10 and interferon (IFN)- were increased after concanavalin-A treatment. However, the upregulation of plasma IL-10 concentration was smaller in the male and female transgenic mice than in the control mice, and the upregulation of the IFN- concentration was greater in the female transgenic mice than in the female control mice.Conclusions Th1 and Th2 immune reactions were deranged after concanavalin-A treatment, with Th1 immunity predominating in transgenic mice expressing osteopontin in hepatocytes; this immunological imbalance may contribute to massive liver necrosis.     

Innate resistance to experimental Trypanosoma congolense infection: differences in IL-10 synthesis by macrophage cell lines from resistant and susceptible inbred mice

BALB/c and C57Bl/6 mice differ in resistance to T. congolense infections. We investigated the production of various cytokines (IL-10, IL-6, TNF-alpha and TGF-beta) by macrophages from these mice. Macrophage cell lines (BALB.BM cells) of BALB/c mice but not (ANA-I cells)of C57BL/6 mice constitutively produced IL-10. Challenge of these cells with trypanosomes induced the production of 50-100 times more IL-10 in BALB.BM cells than in ANA-1 cells. Pre-incubation of the cell lines with IFN-gamma. prior to the trypanosome challenge, further upregulated this IL-10 production in BALB.BM but not in ANA-1 cells. Primary cultures of bone marrow-derived macrophages (BMDM) from BALB/c mice also produced more IL-10 following challenge with IFN-gamma and opsonized trypanosomes than did the C57Bl/6 BMDM. Similarly after challenge with trypanosomes, BALB.BM and BALB/c BMDM produced significantly more IL-6 than did the analogous cells from the C57Bl/6 mice following such challenges. Higher steady state levels of TNF-alpha mRNA accumulated in ANA-1 cells than in BALB.BM cells following challenge with IFN-gamma and opsonized trypanosomes. Findings of this study for the first time indicate a differential regulation of cytokines (IL-10, IL-6 and TNF-alpha) in macrophages of mice that significantly differ in their susceptibility to infections with T. congolense.     

乳腺癌患者外周血CD4^＋CD25^＋ Treg细胞及Th1/Th2类细胞因子水平测定及意义

目的探讨乳腺癌患者外周血CD4＋CD2＋5调节性T细胞（CD4＋CD2＋5Treg）水平变化在肿瘤发生、发展中的作用及机制。方法流式细胞术检测45例健康人（对照组）、44例乳腺良性增生患者（增生组）、61例乳腺癌患者（乳腺癌组）外周血CD4＋CD2＋5Treg水平,ELISA法检测三组Th1类细胞因子IL-2、IFN-γ、TNF-α和Th2类细胞因子IL-6水平;分析CD4＋CD2＋5Treg与肿瘤临床病理特征及细胞因子的关系。结果乳腺癌组TNM分期Ⅲ、Ⅳ期患者外周血CD4＋CD2＋5Treg细胞水平显著高于0~Ⅱ期患者、对照组和增生组,且术后水平显著低于术前（P均〈0.05）;乳腺癌组TNM分期Ⅲ、Ⅳ期患者血清IL-2、IFN-γ、TNF-α水平明显低于0~Ⅱ期患者、对照组和增生组,IL-6水平则反之（P均〈0.05）;乳腺癌组外周血CD4＋CD2＋5Treg细胞水平与IL-2、IFN-γ、TNF-α水平呈负相关（r=-0.579、-0.607、-0.691）,与IL-6呈正相关（r=0.804）,P均〈0.05。结论外周血CD4＋CD2＋5Treg细胞水平与乳腺癌发生、发展有关,可能机制为通过调节Th1/Th2细胞因子平衡参与机体免疫应答。     

日本血吸虫病小鼠脏器Th2相关淋巴因子的动态定位

目的了解感染日本血吸虫后小鼠不同脏器Ｔｈ２相关因子介导的免疫反应。方法采用ＡＢＣ免疫组化法,并用多媒体病理图文定量分析,动态研究感染后ＩＬ４,ＩＬ５,ＩＬ１０的变化。结果在感染小鼠肝脏ＩＬ４,ＩＬ５,ＩＬ１０明显高于正常对照（Ｐ＜０．０１）,并随感染时间的延长而逐步升高;在脾脏ＩＬ４,ＩＬ５,ＩＬ１０亦升高,但其幅度明显较肝脏为低;在结肠ＩＬ４,ＩＬ５,ＩＬ１０随感染时间延长呈缓慢升高趋势。结论感染日本血吸虫病的小鼠,肝脏是Ｔｈ２相关因子免疫应答的主要器官;脾脏是调节免疫的器官;而结肠Ｔｈ２相关因子的升高可能是整体反应的一部分     

耻垢分枝杆菌疫苗对小鼠细胞因子产生及Th1/Th2应答的影响

目的研究以耻垢分枝杆菌(M.S)制备的M.S疫苗对小鼠免疫应答的影响,验证M.S的免疫原性、探讨M.S疫苗的免疫调节作用。方法将BALB/c小鼠随机分成生理盐水对照组和M.S疫苗低、中、高剂量组,每组6只,分别注射生理盐水和不同剂量的M.S疫苗。取小鼠脾细胞或腹腔巨噬细胞体外培养,用酶联免疫吸附测定(ELISA)法检测培养上清中白细胞介素(IL)-2、IL-4、IL-12和γ干扰素(IFN-γ)的含量,分析M.S疫苗对小鼠Th1/Th2类应答的影响。结果(1)生理盐水对照组和M.S疫苗低、中、高剂量组小鼠产生的IL-12分别为(32.6±22.7)、(58.9±18.6)、(77.3±38.0)、(114.7±9.9)pg/m l,M.S疫苗中、高剂量组与生理盐水对照组比较差异有统计学意义(P<0.05)。(2)生理盐水对照组和M.S疫苗低、中、高剂量组小鼠产生的IL-2分别为(5.0±2.6)、(13.4±9.3)、(15.3±9.7)、(22.6±7.5)pg/m l,M.S疫苗高剂量组与生理盐水对照组比较差异有统计学意义(P<0.01)。(3)体外以ConA刺激时,生理盐水对照组和M.S疫苗中剂量组小鼠产生的IFN-γ分别为(662±279)和(807±163)pg/m l,IL-4分别为(407±127)和(101±26)pg/m l,但M.S疫苗组与生理盐水对照组比较差异均无统计学意义(P>0.05);体外以M.S-纯化蛋白衍生物(PPD)刺激时,生理盐水对照组和M.S疫苗中剂量组小鼠产生的IFN-γ分别为(14.0±6.31)和(55.3±32.4)pg/m l,两组比较差异有统计学意义(P<0.05),各组产生的IL-4均在检测限以下。结论M.S具有良好的免疫原性,以此制备的M.S疫苗具有促进Th1类应答、抑制Th2类应答的免疫调节作用。     

Analyses of serum levels of type 1, type 2 and type 3 cytokines reveal multiple abnormalities in lupus‐prone (NZB × NZW) F1 mice

Aim: Inherent in vivo cytokine milieu may help protect normal subjects from developing clinical autoimmunity, whereas changes in cytokine milieu may contribute to the development of lupus‐like autoimmunity. Method: Here, we measured circulating levels of the three prototypic cytokines, type 1 (IFN‐γ and IL‐2), type 2 (IL‐4) and type 3 (TGFβ) in the NZB/NZW F1 model of lupus and MHC‐matched nonautoimmune mice. Results: Our results demonstrate that circulating IFN‐γ and IL‐4 levels were higher and active TGFβ levels were lower in lupus‐prone animals than in nonautoimmune mice. Conclusion: Such an in vivo cytokine milieu may contribute to the development of lupus in NZB/NZW F1 mice and to the nonautoimmune phenotype in normal animals.     

B cell activation in patients with rheumatic disease: association with an increased ratio of Th2: Th1 cytokine secreting cells

Abstract

This minireview examines the pattern of T_h1 and T_h2 cytokine-secreting cells present in the peripheral blood of patients with rheumatic diseases including lupus, myositis, Sjögren’s syndrome and rheumatoid arthritis. The general conclusion is reached that diseases marked by increased B cell activation are characterized by a relative increase in the frequency of peripheral blood mononuclear cells secreting T_h2 versus T_h1 cytokines.     

流式微珠阵列法检测结脑患者Th1/Th2细胞因子表达

目的:运用流式微珠阵列法评价IFN-γ、IL-4在结核性脑膜炎(结脑)中的表达情况,以探讨Th1/Th2平衡状态与其疾病发生发展的关系。方法:采集结脑患者治疗前后的外周血和脑脊液以及健康人的外周血,流式微珠阵列法检测其中IL-4和IFN-γ的浓度,比较各检测指标在各组中差异,并分析差异的意义。结果:结脑患者外周血的IFN-γ浓度较正常对照组低,IL-4浓度无差异;治疗前后外周血中的IFN-γ、IL-4和脑脊液中的IL-4水平均差异无统计学意义,但治疗前后脑脊液中IFN-γ表达差异有统计学意义。结论:与正常对照组及治疗前后相比较,Th1细胞因子IFN-γ在结脑患者的体液中有显著性变化,提示其参与结脑的病理生理过程;流式微珠阵列法能准确检测Th1/Th2细胞因子表达的动态变化。