Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease

BACKGROUND: Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-gamma responses to allergens in atopic subjects. OBJECTIVE: To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. METHODS: PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). RESULTS: Atopic children had significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL-5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in atopic children. CONCLUSION: We show that a polyclonal stimulus induces a reduced Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.     

Plasma levels of Th1/Th2 type cytokine are associated with change of prolactin and GH/IGF-I in hemodialysis patients

Patients undergoing chronic hemodialysis (HD) have an impaired immune system involving both B and T cell-mediated immune responses. Since T helper type 1 (Th1) and type 2 (Th2) cytokines are implicated in regulating the immune responses, while the pituitary hormones, prolactin (PRL) and growth hormone (GH) are known to be involved in the regulation of the immune response, all of them may, therefore, be involved in impaired status. The aims of the present study were to estimate the serum concentrations of Th1-Th2 cytokine, GH, insulin-like growth factor-I (IGF-I) and PRL, and to determine whether there are any correlations between the release of T-cell cytokines and disturbance of hormones in a group of patients on maintenance hemodialysis (MHD). The study included 35 HD patients (23 males and 12 females, mean age 56.8+/-12.8 years) and a control group of 20 age-matched healthy subjects. Baseline serum concentrations of GH/IGF-I, PRL, IL-2, sIL-2R, IFN-gamma, IL-4 and IL-10 were measured in all patients and control subjects. Our results demonstrate that the fasting serum concentration of IGF-I, PRL, sIL-2R and Th1-type cytokine, including IL-2 and IFN-gamma, were significantly higher in HD patients compared to the healthy subjects. GH and Th2-type cytokine including IL-4 and IL-10 levels were slightly reduced, but no significant differences were observed between HD patients and the control group. In the group of HD patients, PRL correlated directly with IFN-gamma and correlated inversely with IL-10; IFN-gamma correlated inversely with IL-4; and GH also correlated inversely with IGF-I and IL-4. However, IGF-I correlated directly with IL-2 and IL-10. These data suggest that the Th1/Th2 imbalance in HD patients with an increase of Th1 type cytokines, associated with the altered GH/IGF-I axis and prolactin and immuno-endocrine dysfunction, probably plays a role in an impaired immune system in HD patients.     

Th1/Th2相关细胞因子基因检测方法的建立

目的：建立检测Ｔｈ１／Ｔｈ２相关细胞因子的方法。方法：设计６对用于ＩＬ－２、ＩＬ－４、ＩＬ－１０、ＩＬ－１３、ＩＦＮγ和β－ａｃｔｉｎ基因扩增的引物,建立可用于Ｔｈ１／Ｔｈ２相关细胞因子检测的ＲＴ－ＰＣＲ技术,同时 口平移法制备６种细胞因子的ｃＤＮＡ探针,建立ＲＮＡ斑点杂交技术。结果：用ＲＴ－ＰＣＲ和ＲＮＡ斑点杂交技术检测２０种肿瘤细胞株,发现１１／２０为Ｔｈ２型细胞因子表达,８／２０为Ｔｈ０型,     

Th1/Th2相关细胞因子基因检测方法的建立①

目的建立检测Th1/Th2相关细胞因子的方法。方法设计6对用于IL-2、IL-4、IL-10、IL-13、IFNγ和β-actin 基因扩增的引物，建立可用于Th1/Th2相关细胞因子检测的RT-PCR技术，同时用切口平移法制备6种细胞因子的cDNA探针，建立RNA斑点杂交技术。结果用RT-PCR和RNA斑点杂交技术检测20种肿瘤细胞株，发现11/20为Th2型细胞因子表达，8/20为Th0型，1/20未检测到细胞因子。结论RT-PCR技术和RNA斑点杂交技术是检测Th1/Th2相关细胞因子的有效方法。     

Th1/Th2 cytokine gene polymorphisms in patients with idiopathic pulmonary fibrosis

We investigated 30 patients with idiopathic pulmonary fibrosis (IPF) and 103 healthy volunteers for the cytokines polymorphisms of the IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor-alpha, interferon-gamma, transforming growth factor-beta, IL-1beta, IL-2, IL-4, and IL-4RA genes. The strongest correlation of a genotype with the disease was found for gene polymorphisms at the promotor region of IL-4, where the CT genotypes at the positions (-590) and (-33) were more frequent in the IPF group (P < 0.0001, P(corr) < 0.0022; vs P < 0.0001, P(corr) < 0.0022). Our results support the idea of the pathogenic role of cytokine gene polymorphisms in the etiology and pathogenesis of IPF, with emphasize on the IL-4 promotor gene polymorphisms.     

Th1/Th2 cytokine responses following HIV-1 immunization in seronegative volunteers

The Th1/Th2 profile that follows human vaccination may profoundly influence the subsequent course of disease after infection. However, the ability to detect IL-4 has been limited outside trials of live vaccination. By using methods in which memory effector cells are allowed to antigenically expand by short term culture, followed by low-dose mitogenic stimulation, we have been able to follow the Th1/Th2 profile in HIV-1^?volunteers enrolled in two phase I studies of HIV immunogens (a recombinant gp120 and a multivalent, octomeric V3 loop peptide). Antigen-specific interferon-gamma (IFN-γ) could be detected in primary stimulation, but IL-4 was observed only after antigenic expansion and restimulation. In both of these studies the responses after initial immunizations were dominated by IFN-γ, with IL-4 appearing only after multiple rounds of immunization, and IL-4 was temporally related to antibody production. Concomitant with the IL-4 production, the amount of supernatant IFN-γ declined. Antigen-specific IL-10 was not detected in either study. Such techniques, which have been shown to correlate with outcomes in immunotherapy, may prove useful as future surrogates of human vaccine response.     

Adult Still's disease reflects a Th2 rather than a Th1 cytokine profile

Adult Still's disease (ASD) is a chronic multisystemic disease. Extraordinarily high serum levels of IL-18 in ASD patients have been described, whereas the mechanism remains to be clarified. This study aimed to evaluate proinflammatory cytokines and to consider their pathological roles. In patients with rheumatic diseases (n = 151), blood samples were taken at the active phase and the serum levels of IL-18 and other proinflammatory cytokines were measured by ELISA. The extra-high levels of IL-18 were confirmed selectively in ASD patients (n = 10). In the active phase of ASD patients, the levels of IL-6 were elevated accordingly, but IL-1beta and TNF-alpha were undetectable. As to Th1-Th2 cytokines, the levels of IL-4 and IL-13, but not INF-gamma, IL-12, or IL-2, were elevated in all ASD patients examined. Moreover, the serum levels of IL-18 showed a good correlation with those of IL-4, suggesting that ASD reflects a Th2 rather than a Th1 cytokine profile.     

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Thl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Thl/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,immune senescence”,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Thl/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Thl/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。     

Th1/Th2 cytokine profile in patients coinfected with HIV and Leishmania in Brazil

To evaluate the effects of HIV on immune responses in cutaneous leishmaniasis (CL), we quantified cytokine levels from plasma and stimulated peripheral blood mononuclear cells (PBMCs) from individuals infected with HIV and/or CL. Gamma interferon (IFN-γ) and interleukin 13 (IL-13) levels and the ratio of IFN-γ to IL-10 produced in response to stimulation with soluble Leishmania antigens were significantly lower in HIV-Leishmania-coinfected patients than in CL-monoinfected patients.     

Th2/Th3 cytokine genotypes are associated with pregnancy loss

Cytokines are critical immunoregulatory molecules, responsible for determining the nature of an immune response. It has been proposed that Th2/Th3 immune reactions support normal pregnancy, while Th1 immunity is considered detrimental to the fetus. Since cytokine production is partly under genetic control, it is possible that women suffering from a high incidence of abortions are genetically predisposed to mount a type of immune response inappropriate for pregnancy maintenance. This study investigated the frequencies of cytokine gene polymorphisms in abortion-prone women and women with successful pregnancies. We investigated the role of Th1/Th2/Th3 cytokine gene polymorphisms, such as TGF-beta1 codon 10 (TGFbetac10; C to T), TGF-beta1 codon 25 (TGFbetac25; G to C), TNFalpha promoter-308 (G to A), IL-6 promoter-174 (G to C), IL-10 promoter-1082 (G to A), IL-10 promoter-819 (C to T), IL-10 promoter-592 (C to A), and IFNgamma intron 1 +874 (A to T) in abortion-prone female patients. Our results support the importance of Th2/Th3 immune responses in pregnancy loss, and suggest that an individual's immunogenetic profile indicative of imbalances in Th2/Th3 cytokines is associated with pregnancy loss. Our results suggest that abortive events are determined by genetic factors, reflected in the female patient's immunogenetic profile.     

High Th1-type cytokine serum levels in patients with infectious mononucleosis

Most adults are asymptomatically infected with Epstein-Barr virus (EBV). Primary EBV infection is commonly associated with acute infectious mononucleosis (IM). T cell immune activation plays an important role in EBV-associated diseases. IM shows a mainly Th1-type profile, so Th1-type cytokines such as interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and lymphotoxin (LT) are moderately enhanced. We measured IL-2 and IFN-gamma in serum during acute phase of the disease and during convalescence. Sera were collected from 23 IM patients, 13 patients with similar clinical manifestations but without IM, and 10 healthy donors. The levels of IL-2, IFN-gamma and IL-12 were significantly higher in patients with acute IM than in healthy individuals. IL-2, IFN-gamma and IL-12 decreased during convalescence. These three cytokines may be useful as sensitive markers of IM during severe illness and its later phases.     

Graft-versus-host disease and the Th1/Th2 paradigm

Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation (BMT) and is initiated by alloreactive donor T cells recognizing foreign histocompatibility antigens of the host. There is now substantial experimental and clinical evidence to implicate a dysregulation of cytokine networks as a primary cause for the induction and maintenance of GVHD. In this article, current knowledge of the involvement of cytokines in GVHD is reviewed. The balance between type 1 cytokines (interleukin-2, interferon-γ) and type 2 cytokines (interleukin-4, interleukin-10) is hypothesized to govern the extent to which a cell-mediated immune response and a systemic inflammatory response develop after allogeneic BMT. Because type 2 cytokines can inhibit the production of the proinflammatory cytokines interleukin-1 and tumor necrosis factor-α, a type 1 to type 2 shift in the initial response of donor T cells to host alloantigens may interrupt the cytokine cascade after allogeneic BMT and may offer a new approach to the prevention and treatment of acute GVHD. Interventions to specifically eliminate or modify the response of donor T cells to alloantigens in order to reduce GVHD may obviate the need for T cell depletion in clinical BMT and thus avoid the increased risk of relapse of malignancy and impairment of donor cell engraftment.     

自身免疫病的Th1/Th2细胞因子平衡治疗

在很多自身免疫性疾病中存在着细胞因子不平衡的现象，导致机体细胞免疫或体液免疫的失调。Ｔｈ１／Ｔｈ２分别介导细胞免疫和体液免疫，可以代表机体复杂的细胞因子网络，从整个评估机体免疫功能。     

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.     

绒毛和蜕膜中的Th1,Th2细胞因子水平与反复流产的关系

目的　了解Th1,Th2细胞因子在反复流产患者绒毛和蜕膜中的浓度以及与反复流产的关系。方法　采用放射免疫的方法 (RIA)对 80例反复流产患者和 2 8例正常妇女的绒毛和蜕膜中Th1,Th2细胞因子进行检测。结果　反复流产患者中绒毛、蜕膜Th1,Th2细胞因子的浓度增高 ,与正常对照组相比 (P <0 0 5 ,0 0 1) ;Th1/Th2偏移。结论　Th1、Th2型细胞因子的异常分布与妊娠丢失有关     

IL-18 time-dependently modulates Th1/Th2 cytokine production by ligand-activated NKT cells

While IL-18 synergizes with IL-12 to induce a Th1 immune response, it also promotes a Th2 response. Here we investigate the modulatory role of IL-18 on the Th1/Th2 cytokine response. The injection of alpha-galactosylceramide (alpha-GalCer), a ligand for NKT cells, elevated mouse serum levels of both IFN-gamma and IL-4. When the mice were treated 2 h before alpha-GalCer challenge with IL-18, IFN-gamma production but not IL-4 production was remarkably up-regulated. In contrast, pretreatment with IL-18 6 h before the challenge enhanced IL-4 production. However, this IL-18-enhanced IL-4 production was not elicited in mice injected with anti-CD3 Ab. Liver mononuclear cells (MNC) produced a similar cytokine production pattern when MNC from mice treated with IL-18 either 2 h or 6 h before challenge were stimulated with alpha-GalCer in vitro. Expression of SOCS1 and SOCS3 was notably up-regulated in the liver MNC from mice pretreated 6 h before with IL-18; in particular, SOCS3 expression was confined to the liver NKT cells. Inhibition of SOCS3 by RNA interference up-regulated the phosphorylation of STAT3 and suppressed in vitro IL-4 production by IL-18-primed liver MNC stimulated with alpha-GalCer, but it did not affect IFN-gamma production. These results suggest that IL-18 time-dependently modulates Th1/Th2 cytokine production in ligand-activated NKT cells by regulating/inducing SOCS3 expression.     

细粒棘球蚴感染对哮喘大鼠血清白介素-17水平及Th1/Th2平衡的影响

目的建立细粒棘球蚴感染并发过敏性哮喘实验动物模型及探讨细粒棘球蚴感染对过敏性哮喘的作用。方法 24只健康Wistar大鼠,随机分为3组,A组为正常对照组,B组为单纯哮喘组,C组为细粒棘球蚴感染并发哮喘组。C组大鼠经腹腔注射感染细粒棘球蚴,70 d后,以卵白蛋白(OVA)分别对B组、C组大鼠进行致敏及激发,建立过敏性哮喘模型。取大鼠肺组织作病理切片,观察大鼠肺组织的炎症变化,采用酶联免疫吸附试验(ELISA)检测大鼠血清白介素-17(IL-17)、白介素-4(IL-4)及干扰素-γ(IFN-γ)的水平。结果与B组比较,C组大鼠血清IL-17和IL-4的水平明显下降(P<0.05),而血清IFN-γ的水平明显上升(P<0.05)。各组大鼠血清IL-4与IFN-γ水平呈密切负相关(r=-0.915),IL-4和IFN-γ水平与IL-17呈负相关关系(r=-0.406,-0.603),P<0.05。结论细粒棘球蚴感染对过敏性哮喘的发生有抑制作用。