Th1/Th2 imbalance in HCV-related liver cirrhosis

The mechanism by which Hepatitis C virus(HCV) infection promotes the development of hepatocellular carcinoma(HCC) is not known exactly. HCV related HCC occurs frequency in the patients with cirrhosis. There have been reports indicating that Th2-type cytokines down-regulated antitumor immunity, and the activation of type 1 T cell responses produced antitumor immunity. We thought Th1/Th2 imbalance in HCV-related liver cirrhosis might be closely related to the development of HCC. In this study, therefore, we investigated the Th1/Th2 balance at the single lymphocyte level of the patients with HCV-related liver cirrhosis and compared with normal controls by using flow cytometry. Th1-type cytokines(IFN-gamma, IL-2) production was significantly decreased in patients with cirrhosis, whereas Th2-type cytokine production(IL-10) was increased. These suggest Th1/Th2 imbalance in HCV-related cirrhosis would decrease the antitumor immunity and its improvement might present the protective effect from HCC.     

Neonatal Th activation

A case is reported of a 1-month-old infant with bowel obstruction and suspected sepsis whose red cells were found to be Th activated during the course of evaluating weakened A antigen activity. Neither Th activation nor weakened A antigen activity was present on the red cells of either parent. The Th activation and the weak reactivity obtained with commercial anti-A reagents were unrelated.     

Th1 and Th2 cytokine responses to academic stress.

Predominant Th2 profiles are associated with the worsening of asthma, and stress is speculated to induce a Th2 profile. The goals of this study were to examine the responses of the cytokines Th1 (IFN-gamma and IL-2) and Th2 (IL-4, IL-5, and IL-6) to a stressor and to look at the relationships between cytokine and psychological responses. Twenty-four students with and without a history of asthma completed questionnaires and gave blood samples during nonexam and exam periods. Cytokines were measured by ELISA from supernatants of stimulated mononuclear cells (MNC) and whole blood. During examinations, there were a significant decrease in IL-2 and a significant increase in IL-6 production (both cultures) and a significant decrease in IFN-gamma production (MNC cultures). Baseline IL-2 levels showed significant negative correlations with several stress and mood scores. Findings of this study indicate a down-regulation of Th1 and a selective up-regulation of Th2 cytokines during a stressful exposure.     

Th1/Th2 cross-regulation and the discovery of IL-10

In the late 1980s, Tim Mosmann and colleagues isolated functionally distinct T helper (Th)-1 and Th2 clones, and provided evidence that these two subsets were mutually inhibitory. Knowledge of the inhibition led to the discovery that Th2 cells make IL-10 to suppress Th1 cells.     

腹腔镜下卵巢型子宫内膜异位囊肿剥除术后T辅助细胞1/T辅助细胞2的动态漂移

目的 研究腹腔镜下卵巢子宫内膜异位囊肿剥除术后Th1(T辅助细胞1)、Th2(T辅助细胞2)各细胞因子的动态变化.方法 2009年7月～2011年8月收住宁夏医科大学附属医院妇科行腹腔镜下卵巢子宫内膜异位囊肿剥除术并经术后病理证实诊断的患者36人,ELISA法检测手术前2d、术后2h、术后72 h血清的IL-2(白介素2)、IL-4(白介素4)、IL-6(白介素6)、IL-10(白介素10)、TNF-α(肿瘤坏死因子α)及IFN-γ(干扰素γ)表达变化.结果 IFN-γ在术后2h下降明显,术后72 h复又升高,且升高程度与术后2h以及术前相比均有统计学差异;IL-4、IL-6在术后2h升高明显,术后72 h下降,且下降程度与术后2h以及术前相比均有统计学差异;IFN-γ/IL-4比值在术后2h下降,与术前相比有统计学差异,而术后72 h比值升高,与术后2h及术前均有统计学差异.结论 腹腔镜下卵巢型子宫内膜异位囊肿剥除术有利于纠正Th2漂移,破坏了有利于异位内膜生长的免疫环境.     

肝细胞肝癌病人Th1/Th2免疫评估

目的 通过检测135例原发性肝癌（PLC）患者手术前后血清IL-2、IL-4、IL-10、IFN-γ、肿瘤坏死因子（TNF）-α水平,并与30例健康查体者（对照组）进行对照分析,观察肝细胞癌病人免疫功能改变并进一步结合临床病理学指标,分析免疫功能变化对临床诊断的指导意义.方法 肝癌病人在术前和术后10d、20d、30d抽取清晨空腹静脉血,对照组在体检合格后抽取空腹静脉血,ELISA技术检测血清IL-2、IL-4、IL-10、IFN-γ、肿瘤坏死因子（TNF）-α浓度.结果 肝癌患者IL-2含量平均为98.2pg/ml,较对照组明显降低（p〈0.05）;IL-4、IL-10含量肝癌组为114.8±27.3 pg/ml和65.6 pg/ml,均明显高于正常对照组（p〈0.01）; TNF-α、IFN-γ血浆含量在肝癌组分别为153.3 pg/ml和89.0 pg/ml,与正常对照组比较均具有显著差异（P〈0.01）.IL-2、TNF-α血清含量在Ⅱ、Ⅲ期肝癌患者均低于Ⅰ期（p〈0.01）,IL-4、IL-10 血浆含量随着病情进展逐渐升高,呈现III期〉II期〉I期趋势,其差异具有显著意义;PHCⅡ、Ⅲ期患者IFN-r含量与Ⅰ期患者间比较差异有显著性.手术后 IL-2、IFN-γ、TNF-α呈逐渐升高趋势,术后20天起血浆浓度与术前血浆浓度相比即具有明显差异（p〈0.05）,术后30天即基本接近正常水平,与术前、术后10天相比具有显著统计学意义（p〈0.05）;IL-4、IL-10呈现逐渐降低趋势,术后20天、术后30天与术前相比其差异具有显著统计学意义（p〈0.05,p〈0.01）.结论 肝癌病人免疫功能失衡,出现Th1/Th2漂移,表现为IL-2、IL-4、TNF-α、IFN-γ、IL-4、IL-10等指标明显改变,并且与肿瘤的分期有关,可作为判断肿瘤分期指标之一.手术切除肿瘤在一定程度上可促进患者免疫失衡的恢复,但手术、麻醉等大的损伤可进一步加重病人的免疫失衡,故不能完全切除病灶者,手术适应症的选择需慎重.     

神经肽Y及Th1/Th2细胞与多发性硬化

目的:近年来国内外有关神经肽Y在免疫学上的作用以及Th1/Th2它们的平衡与免疫性疾病(如多发性硬化)之间的关系的研究较多。另外还有许多基本的问题需要深入探讨:神经肽Y作用于免疫系统的确切机制是什么?多发性硬化等自身免疫性疾病,他们的交感神经系统活性异常增高或很低,神经肽Y对他们的作用又是什么?资料来源:应用计算机检索Medline1994-09/2004-09与神经肽Y,Th1/Th2和多发性硬化相关文章,检索词“neuropeptideY,Th1/Th2cell,Multiplesclerosis,并限定文章语言种类为English。同时计算机检索CNBI1994-09/2004-09期间的文章,限定文章语言种类为中文,检索词“神经肽Y,Th1/Th2,多发性硬化”。资料选择:就检索到的160余篇文献进行筛选,选择以神经肽Y,Th1/Th2细胞为主要研究内容的文献20多篇,无论研究对象为动物还是患者全部纳入,其中研究内容相似的,以近3年且发表在较权威杂志者优先,排除综述类文献。资料提炼:将筛选到的20余篇文献按神经肽Y结构、功能和免疫性疾病关系分类:其中1篇与神经肽Y的结构相关,10篇与神经肽Y及Th细胞的功能相关,9篇与他们和免疫性疾病的关系有关。资料综合:20篇文献共包括730例患者(或实验动物),说明了神经肽Y能影响Th1/Th2细胞的平衡,它能促进Th2细胞分泌白细胞介素4,抑制Th1细胞分泌γ-干扰素,从而可能抑制多发性硬化的发生。结论:Th1/Th2的平衡紊乱可促进多发性硬化的发病,神经肽Y可调节Th1/Th2细胞平衡,与多发性硬化的发病之间有着密切的相关性。     

Th1、Th2、Th17相关细胞因子与儿童系统性红斑狼疮疾病活动程度的相关性研究

目的 检测儿童系统性红斑狼疮(cSLE)血液辅助性T细胞(Th)亚群Th1、Th2、Th17相关细胞因子的表达水平,探讨其与疾病活动程度的相关性,寻找cSLE疾病活动期的潜在生物标志物.方法 选取该院cSLE患儿47例作为观察组.依据SLE疾病活动度评分(SLEDAI评分)将观察组分为非活动期组(18例),活动期组(29例).另选取同期该院健康体检儿童20例作为对照组.采用流式细胞术检测3组研究对象血浆中Th1亚群细胞因子白细胞介素(IL)-2、肿瘤坏死因子(TNF)-α和干扰素(IFN)-γ,Th2亚群细胞因子IL-4、IL-6和IL-10,Th17亚群细胞因子IL-17表达水平,以及CD4+T和CD8+T细胞水平.结果 非活动期组和活动期组TNF-α、IFN-γ、IL-6、IL-10和IL-17水平较对照组升高(P<0.05),活动期组IL-6、IL-10和IL-17水平高于非活动期组(P<0.05).活动期组CD4+/CD8+低于对照组(P<0.05).血清IL-6水平与IL-10、IL-17呈正相关(r=0.415、0.497,P<0.05),IL-10水平与IL-17呈正相关(r=0.402,P<0.05).血清IL-6、IL-10、IL-17水平与SLEDAI评分呈正相关(r=0.373、0.440、0.412,P<0.05).IL-6预测cSLE活动程度的最佳临界值为23.25 pg/mL,曲线下面积(AUC)为0.907(P<0.05);IL-10预测cSLE活动程度的最佳临界值为32.50 pg/mL,AUC为0.853(P<0.05);IL-17预测cSLE活动程度的最佳临界值为33.00 pg/mL,AUC为0.767(P<0.05).结论 血清IL-6、IL-10和IL-17与cSLE疾病活动程度具有相关性,IL-6和IL-10的预测效能高于IL-17,可作为预测疾病活动程度的生物标志物.     

Unequal Death in T Helper Cell (Th)1 and Th2 Effectors: Th1, but not Th2, Effectors Undergo Rapid Fas/FasL-mediated Apoptosis

T helper cell (Th) 1, but not Th2, effectors undergo rapid Fas/Fas ligand (FasL)-mediated, activation-induced cell death upon restimulation with antigen. Unequal apoptosis is also observed without restimulation, after a longer lag period. Both effectors undergo delayed apoptosis induced by a non–Fas-mediated pathway. When Th1 and Th2 effectors are co-cultured, Th2 effectors survive preferentially, suggesting the responsible factor(s) is intrinsic to each population. Both Th1 and Th2 effectors express Fas and FasL, but only Th2 effectors express high levels of FAP-1, a Fas-associated phosphatase that may act to inhibit Fas signaling. The rapid death of Th1 effectors leading to selective Th2 survival provides a novel mechanism for differential regulation of the two subsets.     

Innate immune response in Th1- and Th2-dominant mouse strains

C57BL/6 and BALB/c mice are prototypical Th1- and Th2-type mouse strains, respectively. In the present study, we attempted to characterize the innate immune response of macrophages from these mouse strains. Macrophages from C57BL/6 mice produced higher levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12 than those from BALB/c mice after stimulation with macrophage-activating lipopeptide-2 (MALP-2, a synthetic TLR-2 ligand) or lipopolysaccharide (LPS, a TLR-4 ligand). The augmented IL-12 production by C57BL/6 macrophages increased interferon-gamma and, in contrast, decreased IL-13 production by CD4+ T cells. On stimulation with MALP-2 or LPS, C57BL/6 macrophages produced lysosomal enzyme and nitric oxide, effector molecules for bacterial killing, whereas BALB/c macrophages did not. Bactericidal activity of BALB/c macrophages was impaired relative to C57BL/6 macrophages when cells were infected with live bacteria in vitro. In a murine model of septic peritonitis induced by cecal ligation and puncture (CLP), BALB/c mice failed to facilitate bacterial clearance relative to C57BL/6 mice despite an augmented peritoneal leukocyte infiltration that was associated with increased peritoneal levels of cytokines/chemokines. BALB/c mice exhibited increased plasma and hepatic levels of cytokines/chemokines, resulting in an exaggerated systemic inflammation as determined by acute-phase proteins. Finally, BALB/c mice were vulnerable to CLP-induced lethality relative to C57BL/6 mice. Altogether, innate immune response of macrophages is different between these mouse strains, which may affect the development of Th1 and Th2 adaptive immunity in these strains. Reduced systemic inflammatory response in C57BL/6 mice that may result from an eminent local response appears to be beneficial during sepsis.     

Th1/Th2 cells in inflammatory disease states: therapeutic implications

Inflammation is initiated as a protective response by the host, but can often result in systemic pathology. Among cells of the immune system, T lympho-cytes play a major role in the inflammatory response. T cell inflammation is characterised histologically by an infiltration of mononuclear cells. Key regulators of this response are a subset of T lymphocytes called T helper (Th) cells. These cells secrete soluble mediators called cytokines, which orchestrate the immune response. The appropriate regulation of Th cell immunity is critical in the control and prevention of diverse disease states. This review will focus on the role of Th cells in the inflammatory process involved in allergic disease, diabetes, infectious disease, rheumatoid arthritis, heart disease, multiple sclerosis and cancer. In the area of autoimmunity, in particular, a basic understanding of Th cells and cytokines has contributed to the development of clinically efficacious biological agents. This review also examines current and novel treatment strategies under investigation at present that regulate Th cell immunity, which may result in better treatments for immune-mediated diseases.     

Th1/Th2细胞因子在强直性脊柱炎中的表达及其意义

目的 探讨Th1/Th2细胞因子网络在强直性脊柱炎(As)中的变化及其意义.方法 采用酶联免疫吸附试验(ELISA)法测定AS患者血清和关节液Th1/Th2型细胞因子TNF-α、IL-17、IL-10和IL-4的水平,并与正常对照组比较.结果 AS患者血清TNF-α、IL-17和IL-10水平均显著高于正常对照组,IL-4的水平显著低于正常对照组;AS患者关节液TNF-α、IL-17和IL-4的水平显著高于血清水平.结论 AS患者血清Th1/Th2型细胞因子表达存在异常,为Th1优势型.     

Th1/Th2细胞功能变化在婴幼儿毛细支气管炎中的意义

目的：通过观察婴幼儿毛细支气管炎中T辅助细胞Th1/Th2细胞的功能变化，探讨其在毛细支气管炎中的意义。方法：采用ELISA方法测定毛细支气管炎、非喘息性肺炎患儿外周血中干扰素γ（IFN-γ）、白介素4（IL-4）、血清IgE的浓度。结果：（1）毛细支气管炎患儿IL-4的水平显著高于非喘息性肺炎患儿（M=1.66pg&#183;mL^-1，p5=0.05pg&#183;mL^-1，p95=35.46pg&#183;mL^-1）/（M=0.55pg&#183;mL^-1，p5=0.10，p95=21.71pg&#183;mL^-1）（P〈0.05）。（2）IFN-γ在毛细支气管炎中的水平低于非喘息性肺炎，（M=5.93pg&#183;mL^-1，p5=0.59pg&#183;mL^-1，p95=278.93pg&#183;mL^-1）/（M=18.17pg&#183;mL^-1，p5=0.08pg&#183;mL^-1，p95=495.4pg&#183;mL^-1），差异有统计学意义（P〈0.05）。（3）毛细支气管炎患儿IgE的浓度略高于非喘息性肺炎，（M=71.24，p5=2.35pg&#183;mL^-1，p95=867.13IU&#183;mL^-1）/M=19.58，p5=3.68pg&#183;mL^-1，p95=211.90IU&#183;mL^-1），但差异无统计学意义（P〉0.05）。结论：婴幼儿毛细支气管炎中可能存在Th2优势反应。     

Th1 and Th2 subsets in orthopaedic surgery by single-cell cytokine analysis

Significant immunosuppression can occur following allogeneic blood transfusion or surgery. Cytokine stimulation controls immune responses and determines their type and intensity. Infusion of autologous or allogeneic blood provides elements, including cytokines, which may result in transfusion-associated immunomodulation. This study investigates to what extent autologous/cell salvage transfusions affect levels of intracellular cytokines interferon-gamma and interleukin-4, and if this indicates a shift in the T-helper 1/T-helper 2 cell ratio using a novel method of detecting intracellular cytokines, the Magnetic Activated Cell Sorter Cytokine Secretion Assay (MACS Assay). Comparisons were made between patients receiving autologous blood or no blood transfusion, for pre- and post-operation levels of interferon-gamma and interleukin-4. Interferon-gamma producing T-helper 1 cells decreased post-operatively. Concomitantly, interleukin-4 producing T-helper 2 cells increase. These results demonstrate a measurable shift from T-helper 1 to T-helper 2 cells post-operatively. Secondly, the study showed surgery alone instigates the same level of immunomodulation as autologous/cell salvage blood transfusion in combination with surgery.     

细胞因子Th1/Th2偏移与运动及衰老的关系

背景:很多研究都提示机体衰老和疾病过程中均伴有Th1和Th2细胞因子平衡发生偏离的现象.目的:就运动、衰老和免疫领域的细胞因子与Th1/Th2分化、衰老与Th1/Th2型细胞因子、Th1/Th2型细胞因子平衡在运动延缓衰老中的可能作用方面的研究进行归纳分析.方法:检索1990/2011PubMed数据及万方数据库有关运动、免疫和衰老等方面的文献,英文检索词为"exercise,immunesenescence",中文检索词为"运动,衰老,免疫".排除与研究目的无关和内容重复者.保留42篇文献做进一步分析.结果与结论:随着增龄,老年人易出现T淋巴细胞克隆向Th1亚群分化,进而出现Th1型细胞因子分泌增多,抑制Th2型细胞因子的分泌,破坏了Th1/Th2平衡在机体免疫防御反应的调节中所具有关键性作用,导致糖尿病、肿瘤和自身免疫性疾病等发病率增加.大量研究也证实,运动可以延缓衰老,减少老年性疾病的发生率.是否可以通过Th1/Th2偏移及其偏移的逆转来解释呢?还有待科学实验来予以验证.