卵巢癌患者血浆中Th1/Th2类细胞因子的检测

探讨卵巢癌患者血浆中Th1/Th2类细胞因子失调及其临床意义。方法 :用ELISA法检测了 2 5例卵巢癌及 15例健康妇女血浆中IL - 2、IFN -γ、IL - 6和IL - 10水平。结果 :卵巢癌患者较健康妇女血浆中IL - 2水平明显降低 ,而IL - 6和IL - 10明显升高 ,且这种变化随临床期别的升高更加明显。结论 :卵巢癌患者外周血中Th1/Th2类细胞因子失调 ,在卵巢癌的发生发展中可能起重要作用。     

Th1/Th2类细胞因子与葡萄胎恶变的相关性研究

目的:通过对妊娠滋养细胞疾病患者外周血血清中Th1/Th2类细胞因子的测定,从免疫学角度探讨Th1/Th2类细胞因子预测葡萄胎恶变的价值。方法:收集1997至2001年首次以葡萄胎诊断进行清宫和手术的患者的外周血血清,采用酶联免疫吸附法检测血清中IFN-γ、IL-2、IL-4、IL-10的水平来确定Th1/Th2的活性。结果:与侵葡+绒癌组相比,葡萄胎组IFN-γ含量明显增加(P<0.001),IL-10含量明显降低(P<0.001)。葡萄胎患者中,与非恶变组相比,恶变组Th1类细胞因子(IFN-γ,IL-2)含量呈下降趋势,而Th2类细胞因子(IL-4,IL-10)含量呈增加趋势,4种细胞因子变化均具有统计学差异(P<0.0001)。随着滋养细胞增生程度的增加,4种细胞因子的变化均具有统计学差异,除外IL-4的变化在轻、中度增生组中无统计学意义(P>0.05)。结论:Th1/Th2细胞因子向Th2漂移时,葡萄胎恶变倾向增高。     

Th1/Th2比率变化与子痫前期相关性研究

目的:探讨Th1/Th2比率变化与子痫前期相互关系.方法:采用流式细胞技术分别检测15例正常妊娠孕妇(正常妊娠组)和40例子痫前期患者(子痫前期组)外周血和蜕膜组织中的Th1、Th2及Th1/Th2细胞比率,同时测定其肝、肾功能.结果:①子痫前期组Th1细胞、Th1/Th2比率明显高于正常妊娠组(P<0.01);②外周血Th1/Th2比率与蜕膜Th1/Th2比率间呈显著正相关(r=0.818,P<0.01);③Th1细胞、Th1/Th2比率与肝、肾功能损害呈正相关,且随病情的严重程度有升高趋势.结论:子痫前期患者局部的Th1/Th2比率平衡被打乱,Thl/Th2比率改变可能是其发病的重要原因,在一定程度上也反映了病情的轻重.     

复发性流产患者外周血T淋巴细胞亚群及CD_4~ 辅助性T淋巴细胞亚型的变化

目的　探讨不明原因的复发性流产 (URSA)与T淋巴细胞免疫功能的关系。方法　采用酶联免疫斑点 (ELISPOT)法对 30例URSA患者和 2 4例正常妇女 (对照 )的外周血T淋巴细胞亚群及CD 4 辅助性T淋巴细胞 (Th细胞 )亚型进行检测。结果　与对照相比 ,URSA患者外周血中CD 4 辅助性T淋巴细胞百分率增多 (分别为 45 %、6 0 % ,P <0 0 5 ) ,Th1细胞的百分率升高 (14%与 2 6 % ,P<0 0 1) ,Th2细胞的百分率降低 (2 0 %与 7% ,P <0 0 5 ) ,Th1/Th2细胞比值增大 (0 73与 3 80 ,P<0 0 1)。结论　URSA的发生可能与CD 4 辅助性T淋巴细胞的增多及Th1细胞介导的细胞免疫功能的增强有关。     

介入治疗前后宫颈癌组织局部肿瘤细胞Th1/Th2类因子表达动态变化的研究

目的:研究动脉介入化疗前后宫颈癌组织内肿瘤细胞Th1/Th2类细胞因子表达的动态变化。方法:用免疫组化法检测21例宫颈癌介入治疗前后标本IL-2、IFN-γ和IL-4的表达率及表达强度。结果:介入前,介入治疗后第7天及介入治疗后第14天,IL-2表达率为19.05%、85.71%、19.05%;IFN-γ表达率为28.57%、90.48%、38.10%;IL-4表达率为57.14%、76.19%、28.57%。各项指标3个时间点两两的比较,除介入前与介入后14天无统计学差异(P>0.05),其余均有统计学意义(P<0.01)。结论:介入治疗能有效地逆转癌组织局部肿瘤细胞Th1/Th2类细胞因子的表达,增强肿瘤局部免疫。     

妊娠滋养细胞疾病中Th1/Th2类细胞因子的表达与葡萄胎恶变关系的探讨

目的：探讨妊娠滋养细胞疾病中Th1/Th2类细胞因子的表达及与葡萄胎恶变的关系。方法：以IL-2、IFN-γ代表Th1类细胞因子,以IL-4、IL-10、IL-13代表Th2类细胞因子,以β-actin为内参照,用逆转录聚合酶链反应(RT-PCR)方法检测未恶变的葡萄胎12例,发生恶变的葡萄胎及绒癌38例中不同细胞因子的表达模式。结果：非恶变组IL-2及IFN-γ的表达率较恶变组高(P＜001),细胞因子的表达以Th1类占优势,而恶变组IL-4、IL-10及IL-13的表达率较非恶变组高(P＜005),细胞因子的表达以Th2类占优势。恶变组恶变前后相比较,恶变后IL-4、IL-10、IL-13的表达均有增高的趋势(P＜005)。侵蚀性葡萄胎与不同来源的绒癌之间细胞因子的表达差异无显著性(P＞005)。结论：Th2类细胞因子的高表达在妊娠滋养细胞疾病的发生、发展中起一定作用,Th1/Th2漂移对滋养细胞肿瘤的早期发现、患者预后判断及治疗有一定价值。     

反复自然流产与Th1 Th2细胞因子失衡的研究

目的：探讨Th1/Th2型细胞因子失衡在原因不明反复自然流产（URSA）发生中的作用。方法：采用双抗体夹心酶联免疫吸附实验（ELISA），测定42例原因不明反复自然流产妇女及40例正常经产妇的外周血及蜕膜 中干扰素γ（IEN－γ）和白介素－4（IL－4）的含量。结果：①正常早期妊娠妇女IL－4的诱生水平比正常非妊娠组升高（P＜0．05），反复自然流产妇女IFN－γ的诱生水平比正常非妊娠组升高（P＜0．05），IL－4诱生水平降低（P＜0．05）；②正常早期妊娠妇女的IFN－γ/IL-4的比值比正常非妊娠组下降（P＜0．05），反复自然流产妇女的IFN－γ/IL-4的比值显著升高（P＜0．01），在外周血及蜕膜中的变化是一致的。结论：正常妊娠以Th2型细胞因子反应为主，而在反复自然流产患者中，Th1型细胞因子过度表达，Th1/Th2失去平衡，可能是原因不明反复自然流产发生的原因。     

妊娠高血压综合征患者胎盘辅助性T淋巴细胞1型及2型细胞因子变化的意义

妊娠高血压综合征(妊高征)是严重危害母婴健康的妊娠期并发症，其病因与发病机理尚未阐明。免疫学病因与发病机理是近年研究的重点之一，辅助性T淋巴细胞(Th)1型(Th1)2型(Th2)细胞因子水平及其平衡的变化与妊高征的关系引起了关注。研究表明，先兆子痫患者外周血单个核细胞(PBMC)中白细胞介素(IL)2、1干扰素、肿瘤坏死因子α(TNF-α)等Th1型细胞因子水平增加，而IL4、IL-10等Th2型细胞因子水平减少。     

子痫前期患者血清白细胞介素16水平的变化

子痫前期是严重的妊娠期并发症，其病因及发病机制尚未阐明。近年来的研究认为，过度的炎症反应和辅助性T淋巴细胞（Th）1、2平衡失调，是子痫前期重要的免疫学病理变化。白细胞介素（IL）16是活化免疫细胞释放的多功能细胞因子，能刺激免疫细胞产生多种炎性细胞因子，如IL-6和肿瘤坏死因子（TNF）α，促进T淋巴细胞表达IL-2受体，并抑制IL-4、IL-5等Th2型细胞因子的产生，[第一段]     

Th17/Treg平衡与正常妊娠及子痫前期关系的研究

目的:探讨Th17及CD4+CD25+Foxp3+调节性T(regulatory T,Treg)细胞介导的免疫反应在子痫前期发病中的作用。方法:选取在山东大学齐鲁医院进行产前检查的子痫前期患者25例及正常晚孕期妇女27例,并选取育龄期健康未孕妇女20例。利用流式细胞技术检测3组患者血样中分泌IL-17的Th17及CD4+CD25+Foxp3+Treg细胞亚群占CD4+T淋巴细胞的百分比,并计算Th17/Treg比率,比较其在子痫前期与正常妊娠时的变化;再用酶联免疫吸附试验(ELISA)检测3组患者外周血中IL-17、IL-10、TGF-β1等细胞因子的表达并进行比较。结果:(1)与正常未孕组及正常妊娠组相比,子痫前期患者外周血中分泌IL-17的Th17细胞占CD4+T淋巴细胞百分比明显升高(P<0.01),CD4+CD25+Foxp3+Treg细胞占CD4+T淋巴细胞百分比明显降低(P<0.01);与正常未孕组相比,正常妊娠组Th17细胞的比例明显降低(P<0.01),Treg细胞比例明显升高(P<0.05);(2)子痫前期患者外周血中Th17/Treg比率明显高于正常未孕组及正常妊娠组(P<0.01),正常妊娠组外周血中Th17/Treg比率与健康未孕组相比明显降低(P<0.01);(3)子痫前期患者外周血中IL-17及TGF-β1的TGF-β1表达明显高于正常未孕组及正常妊娠组(P<0.05),而IL-10的表达未见明显差异(P>0.05);与正常未孕组相比,正常妊娠组外周血中IL-17、IL-10及TGF-β1的水平均未见明显变化(P>0.05)。结论:正常妊娠可能依赖于Treg细胞介导的免疫耐受状态,子痫前期患者外周血中Th17/Treg之间的平衡失调而倾向于Th17介导的促炎状态,这一机制可能参与了子痫前期的发生发展。     

Th1/Th2漂移与子宫内膜异位症

子宫内膜异位症(EMs)是妇科常见病,其发病机制尚不明确,机体的免疫状态与其发生发展关系密切.近年来关于Th1/Th2细胞功能与子宫内膜异位症的关系成为研究热点.研究证实,EMs患者体内存在Th1/Th2漂移,机体免疫功能减退,异位内膜细胞发生免疫逃逸继而种植生长.通过追溯Th1/Th2概念并分析Th1/Th2漂移对免疫系统造成的影响,揭示了Th1/Th2细胞功能失衡与子宫内膜异位症发病的关系.纠正机体免疫失调、恢复Th1/Th2平衡成为治疗EMs的可能手段.     

Th1/Th2 balance in preeclampsia

The syndrome of preeclampsia has previously been ascribed to generalized maternal endothelial dysfunction, poor placentation and excessive maternal inflammatory response. Recent reports suggest that preeclampsia is associated with a Th1 predominant profile and may be considered as a failure of the tolerance system allowing the second physiological trophoblastic invasion. In this review, we discuss that Th1 predominant immunity is closely related to inflammation, endothelial dysfunction and poor placentation.     

Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia

Introduction: Preeclampsia is one of the major causes of maternal and neonatal mortality. During pregnancy, the immune system must maintain the tolerance to the fetus, thus changes in the cytokine balance may result in a disturbed pregnancy. T helper cells play an important role in modulation of the immune system and are involved in this cytokine balance.

Objective: Many studies have been performed to study the T cell composition in different compartments during pregnancy, although this is the first study in which T cells are evaluated in umbilical cord blood.

Study design: Intracellular expression of INF-gamma, IL-17, IL-4 and forkhead foxP3 in CD4+ T cells was evaluated in umbilical blood from healthy pregnant and preeclamptic women using a flow cytometer.

Results: Th2 and Treg cells levels were significantly diminished in preeclamptic compared to the healthy women, but no difference in Th1 and Th17 levels were found between both groups.

Conclusions: Our data suggest that the cytokine balance is broken, encouraging the development of an exacerbated inflammatory response. Our results show that there is a shift, in the Th1/Th2, and the Th17/Treg balance, favoring skewness towards a proinflammatory status in the umbilical cord blood in preeclampsia.     

Th1/Th2 cytokines balance--yin and yang of reproductive immunology

For years conception of Th2 overbalance during pregnancy has been a paradigm for immunology of reproduction, while Th1 activity has been presented as unwanted component. Studies concerning Th1/Th2 balance in physiological and complicated pregnancy have been reviewed. Th1 activity during early peri-implantation period, premature and term labour not only accompanies but even predominates over Th2 activity. Th1 activity plays important role in promotion of Th2 response, regulation of placentation process, defense against infections and initiation of delivery. Together with Th2 activity it is necessary component of immunological reactions during pregnancy, both activities being inseparable like yin and yang. So paradigm of "Th1-Th2 cooperation" is much closer to reality than "Th2 phenomenon".     

Placental imbalance of Th1- and Th2-type cytokines in preeclampsia

OBJECTIVES: To characterize the changes in the level of T helper 1 (Th1)- [interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha] and Th2-type cytokine (IL-10) and the ratios of Th1/Th2 (IL-2/IL-10 and TNF-alpha/IL-10) in placentae from women with preeclampsia and women with gestational hypertension. METHODS: Placental levels of IL-2, TNF-alpha, and IL-10 were determined with radioimmunoassay and Th1/Th2 ratios (IL-2/IL-10 and TNF-alpha/IL-10) calculated in the placentae from 22 women with preeclampsia, 15 women with gestational hypertension, and 32 normal term pregnant women. RESULTS: Although preeclampsia had the trend of the increase in the placental levels of IL-2 and TNF-alpha and the trend of the decrease in placental IL-10, there were not significant difference in placental levels of IL-2, IL-10, and TNF-alpha among preeclampsia, gestational hypertension, and normal pregnancy (P > 0.05 for all). Placental ratios of IL-2/IL-10 and TNF-alpha/IL-10 were significantly higher in preeclampsia than in normal pregnancy (P = 0.035 and P = 0.005, respectively). No differences of Th1/Th2 ratios were found between preeclampsia and gestational hypertension and between gestational hypertension and normal pregnancy (P > 0.05 for all). CONCLUSIONS: Alterations of placental balances of cytokines with Th1 predominance were demonstrated in preeclampsia. These associations may offer insights into the pathogenesis of preeclampsia.     

Alterations in Th1/Th2 cytokine concentrations in early neonatal life

Objective:?To determine postnatal changes in neonatal serum concentrations of interferon-γ (IFN-γ), interleukin-4 (IL-4) and its soluble receptor (sIL-4R). Methods:?Forty-five healthyterm neonates, 25 of the neonates' mothers and 27 healthyadults (controls) participated in the study. Cytokine concentrations were measured in blood samples from the umbilical cord, from the neonates on the 1st and 5th dayafter birth, from mothers and from controls. Results:?IFN-γ concentrations were significantlylower in the umbilical cord, compared to concentrations in the controls (p?<?0.04), and increased significantlyfrom the umbilical cord to levels in neonates on day5 (p?<?0.03). In mothers and the umbilical cord, IFN-γ concentrations were dependent on the mode of delivery, being higher after vaginal delivery than after elective Cesarean section (p?<?0.005; p?<?0.006, respectively). IL-4 concentrations in the umbilical cord for 1-day and 5-day neonates were significantlyelevated compared to those in mothers (p?<?0.001; p?<?0.0007; p?<?0.0001, respectively) and controls (p?<?0.05; p?<?0.01; p?<?0.006, respectively). sIL-4R concentrations in all neonatal samples were significantlyelevated compared to those in controls (p?<?0.0001), the highest being found in 1-day-old neonates. A strong negative correlation was found between IL-4 and sIL-4R concentrations in 1- and 5-day-old neonates (r?=??0.48, p?<?0.002; r?=??0.45, p?<?0.0065, respectively). Moreover, IFN-γ/IL-4 ratio increased significantly from the umbilical cord to 5 days of life (p?<?0.03). Conclusion:?Our findings indicate an earlier development of IL-4 than IFN-γ, which could be viewed as a developmental characteristic in the ontogeny of the immune system.     

T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis

In the present study, interleukin (IL)-10, IL-12, IL-17, and IL-23 levels were measured in serum and peritoneal fluid of women with minimal or mild endometriosis and compared with levels in controls without endometriosis. Higher IL-23 levels were encountered in the peritoneal fluid of women with endometriosis, suggesting a possible role of this cytokine in these women's infertility.     

Th1/Th2细胞平衡及NK细胞对胚胎种植的影响

目的:通过研究反复种植失败(RIF)患者与首次移植妊娠成功患者种植窗口期外周血中Th1、Th2型细胞因子及自然杀伤(NK)细胞的表达差异,探讨Th1/Th2细胞平衡及NK细胞对胚胎种植的影响及调节机制。方法:选取2020年3月至2020年9月于山东大学齐鲁医院不孕不育诊疗中心就诊的35例RIF患者(RIF组)和首次行体外受精(IVF)或卵细胞浆内单精子注射(ICSI)助孕即成功妊娠的29例不孕症患者(对照组)。于胚胎移植治疗前的黄体中期采集患者外周血,流式细胞术检测Th1型细胞因子IL-2、IFN-γ、TNF-α,Th2型细胞因子IL-4、IL-6、IL-10以及NK细胞水平。结果:种植窗口期RIF组患者外周血中IL-6及IL-2/IL-10、IFN-γ/IL-10和TNF-α/IL-10比值明显高于对照组,IL-10水平明显低于对照组,差异有统计学意义(P<0.05)。RIF组患者外周血中IL-2、IL-4水平及TNF-γ含量高于对照组,TNF-α含量低于对照组,但差异无统计学意义(P>0.05)。两组患者血清中NK细胞比例无明显统计学差异(P>0.05)。结论:IL-6、IL-10可能参与种植窗口期外周血中Th1/Th2细胞平衡调节,从而影响胚胎的种植。