抗柯注射液对柯萨奇B3病毒感染小鼠自然杀伤细胞活性的影响

目的 :检测 BAL B/ c小鼠在感染柯萨奇 (cox) B3病毒后自然杀伤 (NK)细胞活性的动态变化以及抗柯注射液 (RSF)对其影响。方法 :将小鼠分为正常对照组、病毒对照组、10 m g/ kg RSF组、2 0 mg/ kg RSF组和 30m g/ kg RSF组 ,每组 17只 ,分别在病毒感染后第 3天、8天、12天用乳酸脱氢酶释放法 ,检测各组小鼠外周血的NK细胞活性 ,并将心脏行组织病理检查。结果 :病毒感染后第 3天 NK细胞活性显著升高 (6 7.11± 2 .5 2 ) % ,之后进行性下降 ,第 12天时低于正常 [(42 .2 6± 1.6 1) %∶ (47.79± 4.0 3) % ];RSF对 cox B3病毒感染小鼠的 NK细胞活性有双向调节作用。大剂量 (2 0 mg/ kg和 30 mg/ kg) RSF在第 3天时对增高的 NK细胞活性有抑制作用 ,第 12天时可使降低的 NK细胞活性恢复至正常水平 ;小剂量 (10 mg/ kg) RSF在第 3天时对增高的 NK活性无抑制作用 ,但第 12天时也能使降低的 NK活性恢复至正常。病毒感染第 8天时心肌病变最重 ,小剂量 RSF组心肌病变改善较少 ,大剂量 RSF组改善明显。结论 :RSF调节 cox B3病毒感染后机体的 NK细胞活性可能是其防治病毒性心肌炎的重要机制之一。     

益心饮对感染柯萨奇B3病毒小鼠心肌组织穿孔素和颗粒酶B基因表达的影响

本实验在小鼠急性病毒性心肌炎模型上观察了益心饮对心肌穿孔素和颗粒酶BmRNA表达水平的影响。1 .材料与方法 :雄性Balb/c小鼠、4～ 6周龄、体重 (2 0±2 ) g ,1 2 0只 ,分为正常对照组 ,病毒模型组 ,病毒 黄芪对照组 ,病毒 益心饮低、中、高剂量组 ,每组各 2 0只。除正常对照组外 ,均于实验当日在小鼠腹腔注射柯萨奇B3病毒(CVB3 )稀释液 0 2ml复制病毒性心肌炎动物模型。正常对照组腹腔注射 0 2ml不含病毒的稀释液。实验当日在病毒接种 30min后 ,各组灌胃黄芪注射液 1 0 g·kg-1 ·d-1 、益心饮 2 5g·kg-1 ·d-1 、5g·kg-1 ·d-…     

清心Ⅱ号对病毒性心肌炎急性期小鼠Th细胞分化与凋亡干预作用的研究

目的初步探讨病毒性心肌炎(VMC)急性期Th细胞分化和凋亡的部分调控机制,并观察清心Ⅱ号对上述环节的干预作用。方法4周龄、雄性Balb/c小鼠50只,随机分为正常组、模型组和治疗组。模型组和治疗组小鼠腹腔均接种浓度为1∶2000的含柯萨奇B3病毒(CVB3)的Eagle’sMEM液0.1mL。1h后,正常组与模型组均给予生理盐水灌胃,治疗组给予清心Ⅱ号水溶液灌胃。10d后采集血清、脾细胞和心肌标本,采用光镜观察心肌病理改变。结果病理改变方面:模型组小鼠心肌病变明显,治疗组病理改变明显减轻,正常组无明显病理改变。细胞因子方面:与模型组比较,治疗组小鼠γ-干扰素(IFN-γ)水平显著降低(P<0.01),IL-4、IL-10水平均显著回升。Th细胞分化方面:与模型组比较,治疗组Th1/Th2明显下降(P<0.01),且与正常组比较无统计学意义。Th细胞凋亡方面:治疗组与正常组比较,无统计学意义(P>0.05)。结论VMC急性期脾脏Th细胞亚群之间的平衡关系被打乱,Th细胞凋亡率增加,存在脾脏Th细胞过度凋亡的现象。清心Ⅱ号通过平衡Th1、Th2应答,降低IFN-γ水平,提升IL-4、IL-10水平,减少Th细胞过度凋亡,发挥对VMC的积极干预作用。     

IL-35抑制Th17细胞治疗柯萨奇病毒B3诱导的病毒性心肌炎

目的研究IL-35在柯萨奇病毒B3(CVB3)诱导的病毒性心肌炎小鼠模型心脏中的表达意义。方法通过CVB3感染BALB/c小鼠建立病毒性心肌炎模型为感染组(IF组),给予IL-35治疗的小鼠为IL-35治疗组,感染后给予空载质粒治疗的小鼠为p-FC组,正常组未给予病毒感染并给予生理盐水为对照,感染者为酶联免疫吸附法检测心脏IL-35表达,流式细胞技术检测Th17比例,小鼠心脏组织HE染色后进行心肌炎评分。结果感染CVB3病毒1 d、3 d、5 d和7 d后,BALB/c小鼠体重逐步下降分别为(22.3±4.2)g、(18.3±2.6)g、(17.1±2.4)g和(13.2±1.8)g,心肌炎评分逐步升高分别为0.5、1.5、3.0和4.0,腹腔注射IL-35表达质粒可缓解小鼠体重和心肌炎评分;心脏IL-35表达水平与小鼠体重减轻重量(r=-0.532,P=0.034)和心肌炎评分(r=-0.670,P=0.005)呈负相关;CVB3感染第7 d,经IL-35治疗的小鼠脾脏Th17细胞比例下降(P0.05)。结论在心脏组织表达的IL-35可能通过抑制脾脏Th17细胞治疗柯萨奇病毒B3诱导的病毒性心肌炎。     

急性病毒性心肌炎小鼠心肌中Calpain mRNA表达与心肌细胞凋亡的关系研究

目的检测CMpmn mRNA在柯萨奇病毒B3（Coxsackievirus B3,CVB3）急性心肌炎小鼠心肌组织中的表达,并分析其与心肌细胞凋亡的关系。方法以CVB3单次感染Balb／c小鼠建立急性病毒性心肌炎（n=10）模型,同时设立药物干预组（n=12）及药物对照组（n=10）;同期小鼠腹腔无菌注射等剂量不含病毒的DMEM液作为正常对照组（n=8）。以缺口末端标记法（TUNEL）检测各组心肌细胞凋亡情况,计数凋亡率。用逆转录聚合酶链反应（RT-PCR）方法检测小鼠心肌组织中Calpain-1及Calpain-2 mRNA的表达。结果急性病毒性心肌炎组较正常对照组及药物对照组心肌组织内Calpain-1（P=0．02及P=0．04）和Calpain-2（P〈0．01及P=0．02）mRNA表达升高,心肌细胞凋亡率亦增高（P值均〈0．01）;药物对照组与正常对照组心肌组织内Calpain-1（P〉0．05）和Calpain-2（P〉0．05）mRNA及心肌细胞凋亡率均没有统计学差异（P〉0．05）;药物干预组较正常组心肌组织内Calpain-1（P〈0．01）及Calpain-2（P〈0．01）mRNA表达升高,心肌细胞凋亡率亦升高（P〈0．01）;药物干预组较急性病毒性心肌炎组心肌组织内Calpain-1（P=0．04）及Calpain-2（P〈0．01）mRNA表达升高,心肌细胞凋亡率亦升高（P〈0．01）。各实验组小鼠心肌组织中calpain-1及Calpain-2m RNA的表达水平分别与心肌细胞的凋亡呈正相关。结论柯萨奇B3病毒通过激活心肌组织内Calpain,导致心肌细胞的凋亡,从而参与病毒性心肌炎的发生。     

漏芦提取物对病毒性心肌炎心肌细胞的抗氧化作用观察

将心肌细胞分五组,病毒对照组及漏芦大、中、小剂量治疗组接种柯萨奇B3病毒制作病毒性心肌炎模型,分别加入正常或含5、2.5、1 mg生药/ml的漏芦提取物的生长液,正常对照组加等量正生长液。分别检测各组丙二醛（MDA）水平及超氧化物歧化酶（SOD）活性。结果病毒对照组较正常对照组MDA增高,而SOD活性降低;祁州漏芦治疗组明显降低被感染细胞内MDA含量,升高SOD活性,且呈剂量依赖性。认为漏芦提取物通过其抗氧化作用保护心肌。     

小鼠柯萨奇B3病毒性心肌炎心脏炎症细胞因子基因和蛋白表达及黄芪甲甙干预研究

目的 探讨黄芪甲甙对小鼠柯萨奇B3病毒性心肌炎心脏炎症细胞因子肿瘤坏死因子α、白细胞介素1β、白细胞介素6和白细胞介素10 mRNA表达和蛋白质产生的影响.方法 Balb/c小鼠50只随机分为5组,空白对照组,腹腔无菌注射不含病毒的Eagle's培养基0.1 mL,在腹腔注射病毒培养基30 min后,以生理盐水0.1 mL灌胃,共7 d;病毒性心肌炎对照组,小鼠每只腹腔注射0.1 mL内含1×105TCID50柯萨奇B3病毒的Eagle's培养基,在腹腔注射含病毒的Earle's培养基30 min后,以生理盐水0.1 mL灌胃,共7 d;黄芪甲甙低、中、高剂量干预组,在腹腔注射病毒30 min后,用黄芪甲甙剂量分别为0.07、0.2和0.6 ms/(kg·d)0.1 mL灌胃,共7 d.14 d后处死全部小鼠并取其心脏.心脏组织一半用于逆转录聚合酶链反应法测定心脏细胞因子mRNA表达.另一半用Western blot测定细胞因子蛋白质生成量.结果 空白对照组上述细胞因子均无明显表达,心肌炎对照组肿瘤坏死因子α,白细胞介素1β,白细胞介素6和白细胞介素10 mRNA和蛋白产生均显著高于空白对照组;同心肌炎对照组比较,高剂量黄芪甲甙组的肿瘤坏死因子α,白细胞介素1β.白细胞介素6 mRNA和蛋白生成均显著下降,而白细胞介素10mRNA和蛋白明显升高.结论 黄芪甲甙明显降低小鼠柯萨奇B3病毒性心肌炎心脏的致炎症细胞因子肿瘤坏死因子α、白细胞介素1β和白细胞介素6,而升高炎症保护因子白细胞介素10.     

盐酸阿比朵尔对病毒性心肌炎小鼠的治疗作用

目的探讨盐酸阿比朵尔对病毒性心肌炎的治疗作用。方法以柯萨奇B3病毒构建小鼠病毒性心肌炎模型,灌胃给予盐酸阿比朵尔药液(高、中、低)3个剂量治疗7 d。然后观察各组小鼠生存率、血清心肌酶活性、心脏匀浆的病毒滴度以及心脏切片的病理变化并计算病理积分。结果与病毒对照组比较,治疗组的小鼠生存率明显增加,心肌病毒繁殖量明显降低,心肌酶活性明显下降,心肌炎病灶明显减轻。结论盐酸阿比朵尔对病毒性心肌炎具有一定的治疗作用。     

黄芪对病毒性心肌炎小鼠心脏柯萨奇病毒和腺病毒受体表达的影响

目的:研究黄芪对病毒性心肌炎(VMC)小鼠心脏柯萨奇病毒和腺病毒受体(CAR)表达的影响。方法:建立小鼠VMC模型,将120只小鼠随机分为3组:病毒组、治疗组和正常组。在感染病毒后第0、3、7、14天,无菌取出小鼠心脏分别用RT-PCR法半定量检测CAR的表达。结果:病毒组的CAR表达高于正常组,CAR表达高峰在柯萨奇病毒3型(CVB3)感染后第7天;黄芪治疗后的CAR表达明显降低(P<0.01)。结论:感染CVB3后,心脏组织CAR升高,黄芪可降低CAR的表达,从而减轻CVB3对心肌的损害。     

肾上腺皮质激素对柯萨奇B3病毒感染小鼠心肌的保护作用

目的 探讨肾上腺皮质激素对柯萨奇岛病毒感染小鼠心肌损害的治疗作用。方法将200只4周龄Balb／c小鼠随机分为正常对照组、病毒对照组和病毒感染后早期激素治疗组、中期激素治疗组及晚期激素治疗组，每组加只。在病毒感染后不同时期计算心肌病理积分，空斑形成单位法测定心肌细胞病毒滴度，化学发光法检测血清肌钙蛋白I水平。结果病毒感染后7-10天，柯萨奇B3病毒感染各组小鼠心肌病理积分均显著高于正常对照组，而各感染组之间无显著性差异。病毒感染后14天，中期激素治疗组小鼠心肌病理积分显著低于其他病毒感染组，30天后中期激素治疗组小鼠心肌已完全正常，而其他各组小鼠心肌仍有病变。病毒感染后早期激素治疗组心肌病毒滴度显著高于其他各组，且消失慢。病毒性心肌炎小鼠血清肌钙蛋白I水平显著升高，并与病理变化呈直线正相关。结论肾上腺皮质激素可以明显减轻病毒性心肌炎时心肌的病理损害，对心肌细胞有保护作用，尤以病毒感染中期使用激素治疗疗效最好。     

Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNFα

OBJECTIVES: To evaluate the effect of anti-TNFalpha on the Th1 and Th2 cytokines in patients with spondyloarthropathy (SpA). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with active SpA treated with infliximab (5 mg/kg). For comparison, PBMC were also obtained from 15 healthy controls and 19 patients with active rheumatoid arthritis (RA). After stimulation with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN)gamma were determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cells by flow cytometry. RESULTS: At baseline the percentage of T cells positive for IFNgamma (p=0.020) and IL2 (p=0.046) was decreased in patients with SpA compared with healthy controls, while IL10 (p=0.001) was increased. This cytokine profile, confirmed by the mean fluorescence intensities (MFI), was more pronounced in CD3+/CD8- cells and contrasted with higher IL2 production in RA. NK T cells, characterised by high IL4 and IL10 numbers, were also increased in patients with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFNgamma and IL2 in patients with SpA. Moreover, there was a transient decrease in IL10 and NK T cells in patients with high baseline values, resulting in values comparable with those of healthy controls. This switch in cytokine profile was seen in both the CD3+/CD8- and CD3+/CD8+ subsets. CONCLUSIONS: Before treatment patients with SpA had an impaired Th1 cytokine profile compared with healthy controls and patients with RA. TNFalpha blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine balance. These data confirm the effect of anti-TNFalpha on the immune changes in SpA, and provide insights into the mechanisms involved in TNFalpha blockade.     

Analysis of Th1 and Th2 cytokines expressing CD4+ and CD8+ T cells in rheumatoid arthritis by flow cytometry

OBJECTIVE: A Th1/Th2 cytokine imbalance with a predominance of Th1 cytokines has been suggested to be of pathogenetic importance in rheumatoid arthritis (RA). To evaluate the role of Th1/Th2 cytokines in RA, we used intracellular cytokine flow cytometry to determine cytokine profiles of CD4+ and CD8+ T cells in 34 peripheral blood (PB) and 10 synovial fluid (SF) samples from patients with RA. Results were compared with 10 PB samples from healthy controls (HC) and 5 SF samples from patients with non-RA synovitis. METHODS: After stimulating cells with PMA and ionomycin or alternatively with anti-CD3/CD28 in the presence of brefeldin A, intracellular levels of Th1 [interleukin 2 (IL-2), interferon-gamma (IFN-gamma)] and Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were determined for CD3+CD8- (i.e., CD4+ Th1 and Th2 cells) and CD3+CD8+ (i.e., CD8+ Tc1 and Tc2 cells) T cells. RESULTS: The percentages of CD4+ and CD8+ Th1 and Th2 cytokines producing T cells (PB) were similar in patients with RA and healthy controls (HC), with a clear predominance of Th1 cytokines expressing, T cells. With regard to T cell subsets, IFN-gamma-producing T cells were significantly more frequently detected in the CD8+ subset [CD8+: median 45.1% (RA; p < 0.001), 38.2% (HC; p = 0.009) vs CD4+: 10.8%(RA), 17.0% (HC)]. Conversely, IL-2 was found in a higher percentage of CD4+ T cells [CD4+: median 33.4% (RA), 17.9% (HC) vs CD8+: 23.6% (RA), 12.3% (HC)]. Patients not in disease remission tended to have more IFN-gamma-producing CD8+ and IL-2-producing CD4+ T cells than patients in remission [CD8+: median 45.9% (IFN-gamma) vs 23.0% (IFN-gamma); CD4+: median 34.1% (IL-2) vs 18.2% (IL-2)1. In all PB samples, the proportion of T cells producing the Th2 cytokines IL-4, IL-5, IL-10, and IL-13 did not exceed 2%. Cytokine profiles did not differ between patients receiving immunosuppressive treatment and patients treated only with nonsteroidal antiinflammatory drugs. In comparison to PB, RA SF analysis revealed a significant increase in the percentage of IFN-gamma-producing CD4+ (p < 0.001) and CD8+ T cells (p < 0.001). In addition, the percentage of IL-10-producing CD4+ (p < 0.001) as well as CD8+ T cells (p = 0.001) was significantly elevated in SF. However, production of the other Th2 cytokines (IL-4, IL-5, IL-13) was similar in SF and PB. CONCLUSION: These data indicate similar cytokine profiles of T cells in PB of RA patients and healthy controls, with a strong predominance of Th1 cytokines producing T cells in the CD4+ and CD8+ T cell subset of both groups. PB cytokine profiles did not significantly differ in patients with active and non-active disease or between patients receiving and those not receiving immunosuppressive medication. In SF, the proportion of Th1 and Tcl cells was significantly elevated compared to PB, emphasizing the local importance of these cells for inflammation. CD8+ T cells (Tc1 cells) mainly contributed to the production of IFN-gamma, indicating an underestimated role of this cell subset for local cytokine production. The upregulation of IL-10-producing Th2 and Tc2 cells in SF may reflect an insufficient effort to down-regulate chronic inflammation in the joint. Modifying this cytokine imbalance in the joints may be a promising therapeutic approach in RA.     

Th1/Th2 balance alteration in the clinical course of a patient with acute viral myocarditis.

Cytokines have an important role in the pathogenesis and pathophysiology of myocarditis. In this study, subsets of peripheral helper T lymphocytes (Th) in a patient with acute viral myocarditis were analyzed by 3-color flow cytometry. During the clinical course of myocarditis, the Th1/Th2 ratio of peripheral lymphocytes changed. Th1 was dominant in the acute inflammatory phase during which levels of creatine kinase (CK) increased (day 6), then Th2 levels overtook those of Th1 in the recovery phase during which levels of CK decreased (day 13 and 20). At the time of discharge (day 35), Th1 and Th2 had normalized. Thus, it was speculated that the induction of lymphocytic myocarditis was associated with Th1 dominant status, and recovery was related to Th2 polarity. Th subset imbalances may play an important role in the pathogenesis of acute viral myocarditis and these analyses may be useful for understanding the disease activity of myocarditis.     

Enhanced monocyte Th1 cytokine production in HCV-infected cryoglobulinemic patients

BACKGROUND/AIMS: The etiologic link between chronic hepatitis C virus (HCV) infection and mixed cryoglobulinemia is well established, while its prognostic significance within the context of HCV-related hepatitis is not as clear. Patients with an HCV-related cryoglobulinemic syndrome oft have mild liver disease, an aspect that can be influenced by an individual's Th1/Th2 orientation. Our goal was to document stigmata of differentiate cytokine production in this subgroup of patients. METHODS: Fifteen patients with chronic HCV-related liver disease (CLD) and a cryoglobulinemic syndrome (CRYO) were compared to age/sex matched CLD controls with negative cryocrit. Cultured monocytes were stimulated with either Staphylococcus aureus (SAC) or lipopolysaccharide (LPS). RESULTS: The protein concentrations of TNF-alpha and of the Th1-type cytokines interleukin (IL)-12 and IL-18 were significantly greater in the CRYO group, while IL-10 (a Th2 cytokine) levels were greater in the control group. CONCLUSIONS: The clinical distinctiveness of the two groups was reflected at the cytokine level. The cryoglobulinemic patients studied showed a greater Th1 polarization than their cryoglobulin-negative counterparts. This enhanced production of Th1-type cytokines is seemingly not able to rid the host of infection but may account for a milder course of liver disease.     

Airway infection in stable lung transplant patients is associated with decreased intracellular T-helper type 1 pro-inflammatory cytokines in bronchoalveolar lavage T-cell subsets

Abstract: Current immunosuppression protocols to prevent lung transplant rejection reduce pro-inflammatory and T-helper type 1 (Th1) cytokines. However, Th1 T-cell pro-inflammatory cytokine production is important in host defense against bacterial infection in the lungs. Excessive immunosuppression of Th1 T-cell pro-inflammatory cytokines leaves patients susceptible to infection. To investigate whether pulmonary infection in lung transplant recipients is associated with reduced Th1 T-cell pro-inflammatory cytokines, whole blood and bronchoalveolar lavage (BAL) fluid from 13 stable lung transplant patients with 'culture-negative' BAL and 13 patients with 'culture-positive' BAL was stimulated in vitro , and cytokine production by CD8+ and CD4+ T-cell subsets was determined using multiparameter flow cytometry. In BAL samples, there was a significant decrease in interleukin-2 (IL2) in CD3+ T cells and tumor necrosis factor-α (TNF-α) in CD8+ T cells (but not CD4+) in 'culture-positive' compared with 'culture-negative' transplant patients. There was no difference in blood Th1 T-cell cytokines between 'culture-positive' compared with 'culture-negative' transplant patients. A decrease in Th1 cytokines IL-2 and TNF-α in BAL T-cell subsets is associated with isolation of potentially pathogenic organisms in the lungs in stable lung transplant patients. Excessive immunosuppression of these Th1 T-cell pro-inflammatory cytokines in stable transplant patients may leave them susceptible to infection. Modifying immunosuppression by monitoring intracellular Th1 pro-inflammatory cytokines in BAL T cells may help to improve morbidity and infection rates in stable lung transplant patients.     

特发性血小板减少性紫癜患者治疗前后Th1／Th2水平变化及其临床意义

目的：研究特发性血小板减少性紫癜（ITP）患者药物治疗前后辅助性T淋巴细胞（Th）1/Th2细胞因子水平的变化情况及其临床意义。方法：应用流式细胞仪检测60例ITP患者药物治疗前后干扰素γ（IFN-y）、白细胞介素（IL）-2、IL-4、IL-10水平,分析Th1/Th2细胞因子水平的变化情况,并结合疗效作相关性分析。以60名健康体检者为对照。结果：药物治疗有效的ITP患者治疗后Th1细胞因子IL-2、IFN-1水平较治疗前及对照组均显著升高（P〈0．01）。而Th2细胞因子IL-4及IL-10水平在3组间均无显著性差异（P＞0．051．Th1/Th2比例升高。ITP患者Th1细胞因子IL-2、IFN．叮水平在治疗显效组表达均明显高于良效及进步组和无效组（P〈0．05）,良效及进步组与治疗无效组比较亦有显著性差异（P〈0．05）;经相关性分析,患者的疗效与IFN-γ、IL-2均呈正相关。结论：ITP患者药物治疗后Th1细胞因子IL-2、IFN-γ表达升高,且Th1与ITP患者疗效密切相关。     

Pioglitazone, a peroxisome proliferator-activated receptor gamma activator, ameliorates experimental autoimmune myocarditis by modulating Th1/Th2 balance

OBJECTIVES: The aim of this study is to investigate the effect of Peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand on experimental autoimmune myocarditis (EAM). BACKGROUND: Rat EAM model resembles the giant cell myocarditis in human. Recent studies have suggested that Th1 cytokines are involved in the initiation and progression of EAM, whereas Th2 cytokines are associated with the remission. PPAR gamma, which is a member of nuclear hormone receptor superfamily, has been known to affect not only glucose homeostasis but also immune responses, by regulating the Th1/Th2 balance. METHODS: Lewis rats were immunized with cardiac myosin and divided into three groups: Group N, normal control rats (n = 16); Group E, EAM rats (n = 17); and Group P, EAM rats treated with a PPAR gamma activator pioglitazone (n = 20). RESULTS: Cardiac dysfunction and remodeling were inhibited in Group P compared to Group E. Heart weight/body weight ratio and the degree of inflammation and fibrosis were significantly lower in Group P than in Group E. The mRNA levels of macrophage inflammatory protein-1alpha (MIP-1alpha), which plays an important role in the recruitment of inflammatory cells in the early stage of EAM, were upregulated in the heart of Group E, but not in the heart of Group P. Furthermore, the treatment with pioglitazone decreased the expression levels of proinflamatory cytokine (TNF alpha and IL-1beta) genes and Th1 cytokine (IFN-gamma) genes, and increased the expression levels of Th2 cytokine (IL-4) gene. CONCLUSIONS: PPAR gamma ligands may have beneficial effects on myocarditis by inhibiting MIP-1alpha expression and modulating the Th1/Th2 balance.     

Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes

The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1 cytokine profile, but none of seven Th2 clones, induced TF production and PCA. T-cell blasts from four Th1 activated clones were fixed with paraformaldehyde and added to monocytes in the presence of medium alone or their supernatants. Addition of either fixed Th1 cells or their supernatants induced low TF production (0.2 to 0.6 ng/mL), whereas addition of both resulted in much higher TF synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only interferon-gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4 ng/mL). No TF synthesis was induced by activated and fixed Th2 cells and/or their supernatants, whereas combined addition of fixed Th2 cells and Th1 supernatants or IFN-gamma induced noticeable TF production. The addition of either anti-IFN-gamma antibody or Th2 supernatants to monocytes stimulated with activated and fixed Th1 cells plus their supernatant resulted in a dose-dependent inhibition of TF synthesis, which was partially restored by neutralization of interleukin-4 (IL-4) or IL-10. Addition of recombinant IL-4, IL-13, or IL-10, but not IL-5, inhibited the Th1- induced TF production by monocytes. Data indicate that both CD8+ and CD4+ Th1, but not Th2, T cells can help TF production and PCA. Both cell-to-cell contact with activated T cells and Th1-type cytokines, in particular IFN-gamma, are required for optimal TF synthesis, whereas Th2-derived cytokines (IL-4, IL-13, and IL-10) are inhibitory. This may be of potential interest for future therapeutic strategies.