Regulatory effects of miR-138 and RUNX3 on Th1/Th2 balance in peripheral blood of children with cough variant asthma / 中国当代儿科杂志

OBJECTIVES@#To study the expression levels of microRNA-138 (miR-138) and Runt-related transcription factor 3 (RUNX3) in peripheral blood of children with cough variant asthma (CVA) and their regulatory effects on Th1/Th2 balance.@*METHODS@#Sixty-five children with CVA (CVA group) and 30 healthy children (control group) were enrolled. Peripheral venous blood samples were collected for both groups, and CD4@*RESULTS@#Compared with the control group, the CVA group showed significantly decreased levels of IFN-γ and IL-2 from CD4@*CONCLUSIONS@#MiR-138 regulates Th1/Th2 balance by targeting RUNX3 in children with CVA, providing a new direction for the treatment of CVA.

Respuesta inmune Th1/Th2 en pacientes co-infectados con Helicobacter pylori y helmintos / Immune response Th1/Th2 to Helicobacter pylori and Helminths in co-infected patients

Resumen: Introducción: La inflamación asociada con la infección por Helicobacter pylori (H. pylori) se relaciona con la pro gresión de las lesiones precancerosas gástricas. Las infecciones por helmintos podrían modular la respuesta proinflamatoria a la infección por H. pylori desde un perfil tipo LTCD4+ Th1 hacia una respuesta menos perjudicial tipo LTCD4+ Th2. Objetivo: Caracterizar la polarización de la respuesta inmune tipo LTCD4+ Th1/Th2 de pacientes coinfectados por H. pylori y helmintiasis procedentes de áreas de bajo riego para el desarrollo de cáncer gástrico. Pacientes y Método: Se analizaron 63 pacientes, 40 adultos y 23 niños infectados con H. pylori. La determinación de los perfiles séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) se realizó con Análisis Multiplex (xMAP). La relación entre el estado de coinfección por helmintos en pacientes infectados con H. pylori y la polarización de la respuesta inmune mediada por LTCD4+ Th1 y LTCD4+ Th2, se estudió con un modelo de regresión logístico de efectos mixtos. Resultados: La frecuencia de helmintos fue similar en adultos (15%) y niños (17%). La polarización de la respuesta inmune fue más prevalente hacia el tipo LTCD4+ Th1. Los valores séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1 Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) fueron independientes del estado de infestación por helmintos. Conclusión: La prevalencia de infección por parasitismo intestinal fue alta y la polarización de la respuesta inmune fue predominantemente hacia un perfil tipo LTCD4 + Th1.

Abstract: Introduction: Inflammation associated with Helicobacter pylori (H. pylori) infection is linked to the development of a gastric precancerous lesion. Helminth infections could influence the pro-inflam matory response to such infection from LTCD4+ Th1 to a less harmful LTCD4+ Th2 response. Ob jective: To characterize the polarization of the LTCD4+ Th2 immune response in co-infected pa tients with H. pylori and helminths from low-risk areas for developing gastric cancer. Patients and Method: We analyzed 63 patients infected by H. pylori (40 adults and 23 children). Through the Multiplex Analysis technology (xMAP), we determined the serum profiles of the interleukins asso ciated with the polarization of the immune response of LTCD4+ Th1 (IL-1Β, INF-γ, TNF-α) as well as the LTCD4+ Th2 (IL-4, IL-10, and IL-13). The ratio between helminths co-infection status in H. pylori-infected patients and the polarization of the immune response mediated by LTCD4+ Th1 and LTCD4+ Th2 was assessed using a Mixed Effects Logistic Regression Model. Results: The frequency of helminths was similar between adults (15%) and children (17%). The polarization of the immu ne response was more prevalent in LTCD4+ Th1. Serum values of interleukins associated with the immune response polarization of LTCD4+ Th1 (IL-1Β, INF-γ, and TNF-α) and LTCD4+ Th2 (IL-4, IL-10, and IL-13) were independent of helminths infection status. Conclusion: The prevalence of in testinal parasitic infection was high and the immune response polarization was mainly LTCD4 + Th1.

Immune mechanisms of the active ingredients of Chinese medicinal herbs for chronic prostatitis / 中华男科学杂志

Chronic prostatitis is a common male disease, and its pathogenesis is not yet clear. Most scholars believe that oxidative stress and immune imbalance are the keys to the occurrence and progression of chronic prostatitis. Currently immunotherapy of chronic prostatitis remains in the exploratory stage. This article relates the active ingredients of 5 Chinese medicinal herbs (total glucosides of paeony, tripterigium wilfordii polglycosidium, curcumin, geniposide, and quercetin) for the treatment of chronic prostatitis and their possible action mechanisms as follows: 1) inhibiting the immune response and activation and proliferation of T-cells, and adjusting the proportion of Th1/Th2 cells; 2) upregulating the expression of Treg and enhancing the patient's tolerability; 3) suppressing the activation of the NF-kB factor, reducing the release of iNOS, and further decreasing the release of NO, IL-2 and other inflammatory cytokines, which contribute to the suppression of the immune response; 4) inhibiting the production of such chemokines as MCP-1 and MIP-1α in order to reduce their induction of inflammatory response. Studies on the immune mechanisms of Chinese medicinal herbs in the treatment of chronic prostatitis are clinically valuable for the development of new drugs for this disease.

Expression of progesterone-induced blocking factor in severe preeclampsia and its association with immune tolerance imbalance / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore progesterone-induced blocking factor (PIBF) expression in the placenta and blood of patients with severe preeclampsia and its relationship with immune tolerance imbalance.</p><p><b>METHODS</b>Forty-seven patients admitted between January and December, 2012 were enrolled in this study, including 25 patients with early-onset severe preeclampsia (EOPE) and 22 with late-onset severe preeclampsia (LOPE), with 25 women with normal pregnancy serving as control group. The antenatal blood and postpartum placenta were collected for immunohistochemical staining to detect PIBF expression in the placenta and for testing serum PIBF level using ELISA. Flow cytometry was used to detect the percentage of circulating Th1 and Th2 cells and the Th1/Th2 ratio was calculated.</p><p><b>RESULTS</b>PIBF was expressed in decidual cells, syncytiotrophoblasts and partial cytotrophablasts. The serum PIBF levels were 213.58 ± 44.93 ng/ml in EOPE group, 243.00∓61.19 ng/ml in LOPE group and 273.91 ± 48.57 ng/ml in control group. There were significant differences in serum PIBF, blood Th1/Th2 and placenta PIBF-IOD among the 3 groups (P<0.05). EOPE group had significantly lower serum PIBF, lower llacental PIBF quantity (PIBF-IOD) and higher blood Th1/Th2 than the control group (P<0.05). Serum PIBF in women with severe preeclampsia was positively correlated with placenta PIBF-IOD and negatively with blood Th1/Th2 ratio (P<0.05), but a negative correlation between serum PIBF and 24-hour urinary protein was found only in EOPE group (P<0.05).</p><p><b>CONCLUSION</b>The immune tolerance imbalance mediated by PIBF may participate in the pathogenesis of severe preeclampsia. PIBF, the immune suppressor secreted by lymphocytes of pregnancy women, is also a protective factor against severe preeclampsia, which is expected to be a new target in therapy.</p>

T-Helper Cytokine Profiles in Patients with Kawasaki Disease

BACKGROUND AND OBJECTIVES: Kawasaki disease is an acute systemic vasculitis of which pathogenesis suspected is caused by immune dysregulation. The goal of this study is to evaluate the activation pattern of T helper cell type 1 (Th1) and T helper cell type 2 (Th2) in patients with Kawasaki disease. SUBJECTS AND METHODS: Prospective study of 60 patients (male 36, female 24) with diagnosis of Kawasaki disease were enrolled. One hundred and eighty blood samples from these patients were collected according to the different clinical stages {before initial intravenous immunoglobulin (IVIG), 5 days after initial IVIG, 2 months after initial IVIG}. The plasma level of Th1 cytokines; interferon-gamma (IFN-gamma) & interleukin (IL)-2 and Th2 cytokines; IL-4 & IL-10 were measured by enzyme-liked immunosorbent assay. RESULTS: In all patients, the plasma level of Th1 cytokines (IFN-gamma, IL-2) and Th2 cytokines (IL-4 and IL-10) were markedly elevated during the acute stage of Kawasaki disease. Since then, the plasma level of all these cytokines decreased significantly along with the process of clinical stages. Regardless of the existence of coronary artery lesion or no response to initial IVIG treatment, there were no significant differences between them. CONCLUSION: These data suggest that both Th1 and Th2 cells may be activated simultaneously during the acute stage of Kawasaki disease. Further studies are therefore required to establish the difference of activation pattern of T helper cells between Kawasaki disease and other inflammatory diseases.

Neurotrophins up-express in peripheral blood of allergic rhinitis patients and related to Th2 hypothesis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To detect the expression of NGF, BDNF, NT-3 mRNA in the peripheral blood of patients with allergic rhinitis (AR). And to analyze the correlation between NGF, BDNF, NT-3 mRNA expression and the epidsode of rhinitis through Th-2 Hypothesis.@*METHOD@#This study was a group controlled trial. The expression of NGF, BDNF and NT-3 mRNA were tested by real-time quantitative RT-PCR and the concentrations of IL-4, IL-6, IL-10 and INF-alpha were tested by ELISA.@*RESULT@#The expression of NGF, BDNF and NT-3 mRNA in AR patients were 2.44, 4.46 and 1.78 times the amount of those in the healthy adults, respectively. The increased expression of NT-3 correlated positively with the scores of visual analog scale of AR. The concentrations of IL-4, IL-6 and IL-10, which were 2198 +/- 472 pg/mL, 9407 +/- 703 pg/mL and 3917 +/- 323 pg/mL respectively, were higher than those in the healthy adults. The concentration of INF-alpha was 2198 +/- 472 pg/mL and less than the healthy adults. The increased expressions of NGF, NT-3 were positively related to the increase of IL-4, IL-6 and IL-10.@*CONCLUSION@#The expressions of NGF, BDNF and NT-3 mRNA in AR patients are higher than those in the healthy adults. NGF, BDNF and NT-3 may contribute to the pathogenesis of AR. Moreover, NGF and NT-3 may induce the episode of rhinitis through Th-2 Hypothesis.

Imbalance between Th1 and Th2 cells in cord blood is influenced by maternal allergic rhinitis and associated with atopic dermatitis during the first two years of life / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the influence of maternal atopy on cord blood effector T cells and to identify these biologic markers as predictors of atopic dermatitis (AD).</p><p><b>METHODS</b>Seventy mother-infant pairs were recruited in this prospective birth cohort study. Suspected factors for allergy, including maternal allergic history, total serum IgE, and maternal age at birth, were collected. Mother peripheral blood samples and cord blood were obtained and assayed for the percentage of interferon-γ (IFN-γ) and interleukin 4 (IL-4) producing T cells(Th1 and Th2 respectively) using flow cytometry. Their offspring at the age of 2 years old were evaluated by their dermatologist whether they had AD. Statistical analysis was performed using multiple logistic regression models and receiver-operating characteristic curve was employed to predict atopic dermatitis.</p><p><b>RESULTS</b>Twenty-one allergic and 49 nonallergic mothers were recruited in this study. During the first two years of life, 15.7% children (n = 11) developed a physician-diagnosed AD (all children were the only child in the family). In group with maternal allergic rhinitis, a significantly increased percentage of Th2 was observed in peripheral blood of mother (7.10[1.18;16.1]% vs. 0.37[0.25;0.72]%, U = 10.0, P < 0.05) and cord blood of newborns (1.02[0.57;1.34]% vs. 0.21[0.15;0.42]%, U = 127.5, P < 0.05), respectively. Maternal atopic history did not affect the percentage of Th1 cells in cord blood (0.69[0.40;1.12]% vs.0.50[0.31;0.66]%, U = 361.0, P > 0.05). Children with reduced Th1/Th2 ratio in cord blood had a higher risk to develop AD (OR = 1.72, P = 0.001) . The model including Th1/Th2, maternal allergy, maternal age at birth and maternal total IgE showed high ability to discriminate children with and without AD. AUC was 0.907 (95% CI: 0.804-1.011, P < 0.001).</p><p><b>CONCLUSIONS</b>Elevated IL-4⁺CD4⁺ T cells in cord blood were of relevance with maternal allergic history. Imbalance between Th1 cell and Th2 cell at birth are associated with maternal allergy and promoted subsequent AD development.</p>

Research on different expressions of peripheral blood Th1/Th2 cells in psoriasis patients of blood heat syndrome and of blood stasis syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the correlation between the pathogenesis of psoriasis patients of blood heat syndrome (BHS) and blood stasis syndrome (BSS) and peripheral blood Th1/Th2 cells axis drift, and to observe different expressions of peripheral blood Th1/Th2 cells between healthy subjects and psoriasis patients of BHS and BSS.</p><p><b>METHODS</b>There were 15 patients in the BHS group and 15 in the BSS group. There were 16 patients in the healthy control group. The expressions of CD4+ gamma-interferon (IFN-gamma) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry (FACS). The Th1 main cytokines such as IFN-gamma and Th2 cytokines such as IL-4 in the serum of psoriasis patients of different syndromes were detected by enzyme-linked immunosorbent assay (ELISA). The Psoriasis Area and Severity Index score (PASI) were conducted.</p><p><b>RESULTS</b>FACS results showed that the expression level of CD4+ IFN-gamma+ in the PBMCs was significantly higher in the BHS group than in the BSS group and the healthy control group (P < 0.05). Besides, it was positively correlated with the PASI (P < 0.05). ELISA results showed that the peripheral serum level of IFN-gamma was significantly higher in the BHS group than in the BSS group and the healthy control group (P < 0.05). The plasma level of IFN-gamma was positively correlated with the PASI score in the BHS group (P < 0.05). The plasma level of IFN-gamma was negatively correlated with the PASI score in the BSS group (P < 0.05). The peripheral serum level of IL-4 was significantly lower in the BHS group than in the BSS group and the healthy control group (P < 0.05).</p><p><b>CONCLUSIONS</b>Peripheral Th1 cells had dominant state in psoriasis patients of BHS. When psoriasis patients of BHS were transformed to BSS or to the normal level, the expression of peripheral blood Th1 cells decreased.</p>

Effect of Scoparone on Th1/Th2 cytokines and IgE in the experimental allergic rhinitis rats / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To observe changes of serum Th1/Th2 cytokines and IgE of rats with experimental allergic rhinitis (AR) treating with Scoparone (20 ml/kg, the concentration is 168 mg/L).@*METHOD@#Forty male SD rats were randomly divided into 4 groups : group NC, group AR, group Sco, group Dxm. The rats were sensitized with OVA and were then treated with Scoparone, during the treatment, the behaviors were observed and the change in nasal mucosa were recorded. The level of serum cytokines IFN-gamma, IL-4, IL-5 and IgE were determined by ELISA.@*RESULTS@#The behavior scores of group Sco were significantly lower than those of group AR, the difference was statistically significant (P 0.05). The nasal inflammation of group Sco was significantly less than that of group AR. The level of serum IFN-gamma of group Sco was significantly higher than that of group AR, while the levels of serum IgE, IL4, IL-5 of group Sco were significantly lower (P 0.05).@*CONCLUSION@#Scoparone is highly effective in treating allergic rhinitis by regulating the expression of Th1/Th2 cytokines and IgE.

The research on xiaochalhu decoction improving the inflammation of chronic glomerulonephritis patients and relieving the proteinuria / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the balance of T help cell1/2 (Th1/Th2), the changes of correlated proinflammatory cytokines (IFN-gamma and IL-4), and regulated on activation normal T cell expressed and secreted (RANTES), and the abnormal expression of IL-17, the effector of T help cell17 (Th17) in chronic glomerulonephritis (CGN)patients with Shaoyang disease, thus revealing the mechanisms of Xiaochaihu Decoction (XD) for treating proteinuria of CGN patients according to the theory of mediating Shaoyang meridian.</p><p><b>METHODS</b>Totally 70 CGN patients with Shaoyang disease were randomly assigned to two groups, the treatment group (treated by XD) and the control group [treated by Shenyan Kangfu Tablet (SKT)], 35 in each group. Besides, 20 healthy volunteers were recruited as the healthy control group. Besides, routine therapy of chronic kidney disease (CKD), patients in the treatment group and the control group were treated with XD and SKT respectively for 4 weeks. The changes of Chinese medical syndrome, the effectiveness, 24-h urinary protein, renal functions, the peripheral blood IFN-gamma, IL-4, Th1/Th2, IL-17, and RANTES were compared.</p><p><b>RESULTS</b>Before treatment the Th1/Th2, IL-17, and RANTES of the two treated groups were higher, and the IL-4 level was lower than those of the healthy control group (P < 0.05). After treatment the improvement of Chinese medical syndrome, main symptoms, the effectiveness was better in the XD group than in the SKT group (P < 0.05, P < 0.01). The proteinuria obviously decreased in the treatment group, with the efficacy superior to the SKT group (P < 0.05). The Th1/Th2, IL-17, and RANTES decreased to various degrees when compared with the SKT group (P < 0.05, P < 0.01). The IL-4 level increased more obviously in the treatment group than in the control group (P < 0.05). There was no statistical difference in the improvement of the renal function (P > 0.05).</p><p><b>CONCLUSIONS</b>The immune disorder of the CGN patients with Shaoyang disease was correlated with Th1/Th2 imbalance, and abnormal changes of Th17 cell functions and RANTES. XD could improve the inflammation by regulating the immune disorder of CGN patients with Shaoyang disease, which proved that the theory of mediating Shaoyang meridian could be used to improve the inflammation of CGN patients, thus relieving the proteinuria.</p>

Effects of qingyang toujie mixture in combination with prednisone tablet on Th1/Th2 cytokines in patients suffering from systemic lupus erythematosus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To research the effects of Qingyang Toujie Mixture (QTM) in combination with prednisone tablet on the balance of Th1 and Th2 (Th1/Th2) of systemic lupus erythematosus (SLE) patients of yin deficiency syndrome (YDS).</p><p><b>METHODS</b>Totally 42 patients with SLE were recruited from clinics of internal medicine and hospitalization department of First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine from August 2009 to March 2011. They were randomly assigned to the treatment group (22 cases) and the control group (20 cases) according to the random digit table. Another 12 healthy subjects were recruited as the healthy control group from employees of First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine and healthy students in physical examinations. All patients took prednisone tablet. The dosage was adjusted according to the severity of SLE activity index and the condition: 40 -60 mg per day for severe active stage; 20-40 mg per day for moderate active stage; 15 -20 mg per day for light active stage; and less than 15 mg per day for those in the stable stage, respectively. When patients' condition had been stabilized for 1 to 2 weeks, the dosage was gradually reduced according to the method of hormone reduction. In case of the recurrence of symptoms or when complicated with lupus nephritis or lupus encephalitis uncontrollable, standard shock therapy with Cyclophosphamide Injection (0.5-1 g/m2 body surface area, intravenous dripping, once every 4 weeks) was performed. Patients in the treatment group took QTM additionally, one dose daily, taken in two portions, once in the morning and once in the evening. Those in the control group took placebos additionally, one dose daily, taken in two portions, once in the morning and once in the evening. The therapeutic course was 6 months for all. No measure was taken for those in the healthy control group. Venous blood was withdrawal before and after treatment. Th1 cytokines (IFN-gamma, IL-12) and Th2 cytokines (IL-10, IL-4) were detected by ELISA.</p><p><b>RESULTS</b>Compared with the healthy control group, the serum Th1 cytokines such as IL-12 and IFN-gamma, Th2 cytokines such as IL-10 and IL-4 increased, the Th1/Th2 ratios such as IFN-gamma/IL-4 and IL-12/IL-10 decreased in the treatment group and the control group before treatment (P < 0.01). Compared with before treatment in the same group, the serum Th1 cytokines such as IL-12 and IFN-gamma decreased, the serum Th2 cytokines such as IL-10 and IL-4 decreased, the ratios of Th1/Th2 cytokines such as IFN-gamma/IL-4 and IL-12/IL-10 increased in the treatment group (all P < 0.05). Compared with the control group after treatment, IL-4 decreased, and the ratio of IFN-gamma/IL-4 increased in the treatment group (P < 0.05). Fewer patients suffered from adverse reactions in the treatment group than in the control group (P < 0.01).</p><p><b>CONCLUSION</b>QTM in combination with prednisone tablet was effective to improve the balance of Th1/Th2 cytokines, and alleviate the toxic and adverse reactions of hormone or immune inhibitors.</p>

Research on the relationship between chinese medical syndrome types and Th1/Th2 in bronchioloalveolar carcinoma by thoracoscopic technique / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the relationship between Chinese medical syndrome types of bronchioloalveolar carcinoma (BAC) and Th1/Th2.</p><p><b>METHODS</b>Totally 60 BAC patients were syndrome typed as qi and yin deficiency syndrome (QYDS) and qi stagnation and phlegm-blood stasis syndrome (QSPSS), 30 cases in each group. Meanwhile, 30 subjects with benign pulmonary nodules were recruited as the control group. The contents of interferon-gamma (INF-gamma), interleukin 4 (IL-4), IL-2, and IL-5 were detected using thoracoscopic technique.</p><p><b>RESULTS</b>As for Th1 (INF-gamma and IL-2), it was ranked from high to low as the control group > the QSPSS group > the QYDS group (P < 0.05). As for Th2 (IL-4 and IL-5), it was ranked from high to low as the QYDS group > the QSPSS group >the control group (P < 0.05). As for Th1/Th2 (INF-gamma/lL-4, IL-2/IL-5), it was ranked from high to low as the control group > the QSPSS group >the QYDS group (P < 0.05).</p><p><b>CONCLUSIONS</b>Compared with the tissue of benign nodules, Th1 function in tumor tissue of BAC patients was weaker and Th2 function stronger. Chinese medical syndrome types of BAC had correlation with Th1/Th2. Patients of excess syndrome had stronger immunity with Th1/Th2 shifting left,while those of deficiency syndrome were predispose to humoral immunity with Thl/Th2 shifting right.</p>

Effect of Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood on the Th1/Th2 immune balance in peripheral blood in patients with primary Sjogren's syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood on the expression of interferon-γ (IFN-γ)/interleukin-4 (IL-4) in peripheral blood and disease activity in primary Sjogren's syndrome (pSS) patients, and to study the relationship between the immune balance of Th1/Th2 and the disease activity.</p><p><b>METHODS</b>A total of 66 pSS patients were randomized with tossing coins method into two groups: the integrative therapy group (34 cases) and the control group (32 cases); and 28 healthy subjects were taken as the normal group. The integrative therapy group was treated by Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with hydroxychloroquine sulfate tablets and the control group was treated with hydroxychloroquine sulfate tablets. The treatment course was 3 months for both groups. The levels of serum immunoglobulin G (IgG), erythrocyte sedimentation rate (ESR), IFN-γ and IL-4 in peripheral blood were measured before and after treatment.</p><p><b>RESULTS</b>Compared with the normal group, the levels of IgG, ESR, IFN-γ and IL-4 were significantly increased in pSS patients (P<0.05). Remarkably, after 3 months of treatment, these levels were dramatically decreased in both the integrative therapy group and the control group, although still higher than the normal group. The levels of IgG, ESR, IFN-γ and IL-4 in the integrative therapy group were lower than the control group and the same group before treatment (P<0.05). The ratio of IFN-γ/IL-4 also significantly decreased after treatment. Moreover, the level of IFN-γ and the ratio of IFN-γ/IL-4 in the integrative therapy group were significantly lower than the control group (P<0.05). For all patients the ratio of IFN-γ/IL-4 before and after treatment was positive correlated with the levels of IgG and ESR.</p><p><b>CONCLUSION</b>Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood can alleviate the disease activity of pSS by regulating the immune balance of Th1/Th2.</p>

Effects of ozone exposure on percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells and mRNA expression of Foxp3 in asthmatic rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of low-concentration ozone exposure on the percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells and the mRNA expression of transcription factor Foxp3 in asthmatic rats.</p><p><b>METHODS</b>Sixty male Wistar rats were randomly divided into 4 groups (n = 15 for each): normal control group, ovalbumin (OVA) exposure group, ozone exposure group, and OVA+ozone exposure group. The OVA exposure group was sensitized and challenged with OVA to establish an asthma model; the normal control group inhaled aerosolized saline; the ozone exposure group inhaled low-concentration ozone; the OVA+ozone exposure group inhaled low-concentration ozone before being challenged with aerosolized OVA every day. The percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells in CD4(+) T cells was determined by flow cytometry. The levels of interferon-γ (INF-γ) and interleukin 4 (IL-4) in peripheral blood and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA expression of Foxp3 in lung tissue was measured by PCR.</p><p><b>RESULTS</b>The percentages of CD4(+)CD25(high)Foxp(3+) regulatory T cells in OVA exposure group (6.12±1.03%) and ozone exposure group (5.87±1.26%) were significantly lower than that in normal control group (9.85±1.34%), and the percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells in OVA+ozone exposure group (3.31±0.85%) was significantly lower than those in normal control group and OVA exposure group (P < 0.01). The levels of IL-4 in plasma and lung tissue in OVA exposure group (plasma: 21.83±5.12 ng/L; lung tissue: 0.89±0.13 ng/L) were significantly higher than those in normal control group (plasma: 10.58±2.73 ng/L; lung tissue: 0.32±0.11 ng/L) (P < 0.01). The levels of IL-4 in plasma and lung tissue in OVA+ozone exposure group (plasma: 35.47±7.24 ng/L; lung tissue: 1.50±0.42 ng/L) were significantly higher than those in normal control group and OVA exposure group (P < 0.01). The levels of INF-γ in plasma and lung tissue in OVA exposure group (plasma: 61.78±23.45 ng/L; lung tissue: 0.69±0.21 ng/L] were significantly lower than those in normal control group [plasma: 158.89±60.23 ng/L; lung tissue: 1.86±0.29) (P < 0.01). The levels of INF-γ in plasma and lung tissue in OVA+ozone exposure group (plasma: 10.28±2.63 ng/L; lung tissue: 0.41±0.12 ng/L) were significantly lower than those in normal control group and OVA exposure group (P < 0.01). The mRNA expression of Foxp3 was significantly lower in the OVA+ ozone exposure group than in the normal control group (P < 0.05).</p><p><b>CONCLUSION</b>Low-concentration ozone exposure may decrease the number of CD4(+)CD25(high)Foxp(3+) regulatory T cells and inhibit the mRNA expression of Foxp3 to promote Th1/Th2 imbalance in asthmatic rats, suggesting that ozone exposure may be one of factors that induce asthma attack.</p>

All-transretinoic acid regulates Th1/Th2 balance in CD4+ T cells when GATA-3 is deficient / 生物医学与环境科学（英文）

The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on Th1-Th2 balance modulation. However, it is unclear whether or not vitamin A can regulate Th1-Th2 balance under a strong Th1-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite all-trans retinoic acid (ATRA) on Th1-Th2 differentiation in CD4+ T cells under GATA-3 deficiency, which can induce Th1-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4+ T cells and normal CD4+ T were treated for 48 h with or without ATRA. The expression of Th1 and Th2 cytokines were detected by qPCR and ELISA. The results would contribute to clarify the knowledge of the role of vitamin A in regulating Th1-Th2 balance under some special conditions, and help to explain the mechanism of immune regulatory function of vitamin A.

Effect of yangyin yiqi huoxue recipe on immune balance of Th1/Th2 in serum and submaxillary glands of NOD mice with Sjogren's syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Yangyin Yiqi Huoxue Recipe (YYHR) on expression of interferon-gamma (IFN-gamma), IL-2, IL-4, IL-10, and immune balance of Th1/Th2 in serum and submaxillary glands of non-obese diabetic (NOD) mice with Sjogren's syndrome (SS), and to explore its mechanisms.</p><p><b>METHODS</b>Totally 32 NOD mice were randomly into 4 groups, i.e., the model group, the Chinese medicine group [CM, administered with YYHR at the dose of 0.4 mL by gavage (100 g/kg)], the Western medicine group [WM group, administered with hydroxychloroquine 0.4 mL by gavage (60 mg/kg)], and the combined group [administered with YYHR (50 g/kg) and hydroxychloroquine (60 mg/kg) 0.4 mL by gavage], 8 mice in each group. Eight Balb/C mice were recruited as the normal control group. Mice were sacrificed to withdraw blood after 8 weeks. The submaxillary gland was excised. Serum levels of IFN-gamma, IL-2, IL-4, and IL-10 were detected by ELISA. Protein expression of IFN-gamma, IL-2, IL-4, and IL-10 in submaxillary glands was detected by SP method.</p><p><b>RESULTS</b>Compared with the normal group, levels of IFN-gamma, IL-2, IL-4, and IL-10 in serum and submaxillary glands all increased in the model group (P < 0.05). Levels of IFN-gamma and IL-10 in serum in the CM group and the combined group were lower than those of the WM group (P < 0.05). Serum levels of IFN-gamma and IL-2 in submaxillary glands in combined group were lower than those of the WM group (P < 0.05). The ratio of IFN-gamma/IL-4 in serum and submaxillary glands in the model group were higher than that of the rest groups (P < 0.05). Besides, it was the nearest to that of the normal group.</p><p><b>CONCLUSIONS</b>YYHR could decrease the levels of Th1 and Th2 related cytokines and the ratio of IFN-gamma/IL-4 in serum and submaxillary glands of NOD mice with SS. It could achieve therapeutic effects through adjusting immune balance of Th1/Th2 in SS mice.</p>

Hepatitis B e antigen from chronic hepatitis B patients induces Th1/Th2 cytokine imbalance in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the immunoregulatory effect of hepatitis B virus (HBV) e antigen (HBeAg) on peripheral blood monocytes (PBMCs).</p><p><b>METHODS</b>PBMCs were isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in secreted cytokines were measured by enzyme-linked immunosorbent assay of the supernatants. Comparisons between two groups were made by the independent-samples t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was evaluated by Spearman's correlation analysis.</p><p><b>RESULTS</b>Exposure to HBeAg led to a significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190 respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy controls' samples, the HBeAg exposure led to increased levels of secreted cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC-specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05 respectively). Compared to the HBeAg-negative CHB patients' and healthy controls' samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell-specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01 respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and 4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD-1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than 0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was significantly higher in the samples from HBeAg- CHB patients than from the healthy controls (t = 3.214, P less than 0.01).</p><p><b>CONCLUSION</b>HBeAg was able to down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD-L1on monocytes. These changes are conducive to the formation of immune tolerance to HBV. Therefore, HBeAg may play an important role in immune tolerance to chronic HBV infection.</p>

Effects of antihistamine treatment on immune function in rats with experimental hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of antihistamine treatment on immune function in rats with experimental hepatitis.</p><p><b>METHODS</b>Thirty Wistar rats were randomly allocated into three groups:experimental hepatitis group (EH group), antihistamine treatment group (AH group) and normal control group (NC group). Rats in the EH group received the subcutaneous injection of 40% carbon tetrachloride oil solution and were fed on diet with low-protein, low-choline, high-fat and high-alcohol,while rats in the AH group received antihistamine treatment(ketotifen + vitamin C) additionally.They were sacrificed after 4 weeks, and the levels of serum alanine aminotransferase(ALT), total bilirubin (TBil), histamine(HA), IFNgamma, IL-12, IL-4 and IL-10 were determined. The levels of IL-12 mRNA and IFN-gamma mRNA in liver tissue were determined via real-time reverse transcriptional polymerase chain reaction(RT-PCR).</p><p><b>RESULTS</b>(1) Compared to the NC group, in the EH group, the levels of ALT, TBil, and circulating and intrahepatic HA were significantly increased(P less than 0.05); intrahepatic HA were significantly decreased(P less than 0.05) after antihistamine treatment. (2) Compared to the NC group, in the EH group, the levels of IL-4, IL-10 were significantly increased((0.504+/-0.202)ng/ml and (29.025+/-1.478) pg/ml vs (0.811+/-0.244)ng/ml and (33.72+/-4.293)pg/ml respectively, P less than 0.05), and the levels of IL-12 were decreased ((6.515+/-2.893)pg/ml vs (3.519+/-1.113)pg/ml, P less than 0.05); and after antihistamine treatment the levels of IL-4 and IL-10 were significantly decreased (were (0.423+/-0.168)ng/ml and (30.412+/-3.275)pg/ml, P less than 0.05), the levels of IL-12 were significantly increased (P less than 0.05), but the level of IFNgamma had no significance (P more than 0.05). The levels of intrahepatic IL-12 mRNA and IFNgamma mRNA had similar results.</p><p><b>CONCLUSION</b>Antihistamine treatment may improve liver function and correct Th1/Th2 unbalance.</p>

Effects of transcription factor T-bet, GATA-3, FoxP3 and CD4(+)CD25(+)regulatory T cells in pathogenesis of child Hench-Schonlein purpura / 中国实验血液学杂志

The aim of this study was to investigate the effects of transcription factors T-bet, GATA-3 in the pathogenesis of Hench-Schonlein purpura (HSP) in children, the relationship between CD4(+)CD25(+)regulatory T cells, transcription factor FoxP3 and the development of child HSP, and the molecular mechanisms of Th1/Th2 imbalance of child HSP at acute phase, so as to may provide a new approach and strategy for the treatment of HSP at the molecular levels. The expression of T-bet, GATA-3 and FoxP3 mRNA were detected by real time PCR using SYBR Green I in 46 patients with HSP at acute phase and 30 healthy children as controls. The expression of T lymphocyte subsets CD4(+)CD25(+) in peripheral blood mononuclear cells was detected by flow cytometry. The results showed that the relative level of GATA-3 mRNA in peripheral blood mononuclear cells of patients with HSP was significantly higher than those of the control group (964.30 ± 655.18 vs 78.09 ± 57.20, P < 0.01). The relative level of T-bet mRNA in peripheral blood mononuclear cells of patients with HSP was lower than those of the control group (53.98 ± 35.79 vs 181.56 ± 96.90, P < 0.01). The expression level of FoxP3 mRNA with HSP was lower than that of the control group (32.17 ± 23.04 vs 147.91 ± 99.15, P < 0.01). The result of CD4(+)CD25(+) Treg with HSP was lower than those of the control group [(5.34 ± 2.51)% vs (7.85 ± 1.97)%, P < 0.01)]. It is concluded that Th1/Th2 imbalance exists in acute phase of child HSP, especially predominant activation of Th2, which correlates with the abnormal expression of transcription factor T-bet and GATA-3 mRNA. At acute phase of child HSP, the expression of CD4(+)CD25(+)Treg and its special transcription factor FoxP3 mRNA are down-regulated. Treg cells decreases, which indicates that insufficient immunosuppressive effects resulting from the reduction of Treg cells may be one of the important reason in the immune imbalance of HSP acute phase. This study provides experimental evidence for illustrating the pathogenesis of HSP from the molecular mechanism of Treg cells and its regulation, and also provides a new thinking and new strategies for the treatment of HSP at molecular levels.

Xiaoyin recipe ( ) for psoriasis induces a Th1/Th2 balance drift toward Th2 in peripheral blood mononuclear cells of experimental autoimmune thyroiditis rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the regulatory mechanism of Xiaoyin Recipe () on the T helper 1/T helper 2 (Th1/Th2) immune balance.</p><p><b>METHODS</b>Thirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Th1-Th2-Th3 Microarray. The expressions of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Gene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27rα), glomulin (Glmn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF-α mRNA (P<0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P <0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P <0.01), while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P <0.01).</p><p><b>CONCLUSION</b>Xiaoyin Recipe for psoriasis could induce a Th1/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.</p>