妊高征患者血清肿瘤坏死因子和白细胞介素-8的检测

妊高征是严重危害孕产妇健康的疾病。近年来，肿瘤坏死因子（ＴＮＦ）和白细胞介素（ＩＬ）与异常的免疫激活及内皮细胞损伤的研究愈来愈受到重视［１，２］。为探讨ＴＮＦα和ＩＬ８与妊高征的关系，我们应用酶联免疫方法测定５３例妊高征孕妇和３５例正常孕妇的ＴＮ...     

两种细胞因子在早产儿与足月儿脐血中的表达

目的：探讨早产儿及足月儿出生时免疫功能的变化。方法：采用细胞原位杂交技术，对早产儿１６例（观察组）和足月儿１８例（对照组）出生时脐血的白细胞介素－１β（ＩＬ－１β）和白细胞介素－１受体拮抗剂（ＩＬ－１ｒα）基因表达水平进行分析。结果：观察组中，胎膜早破自娩的新生儿ＩＬ－１β和ＩＬ－１ｒα的ｍＲＮＡ表达明显低于观察组中妊高征剖宫产新生儿和对照组（Ｐ＜０．００１）。而观察组中妊高征剖宫产新生儿ＩＬ－１β和ＩＬ－１ｒα的ｍＲＮＡ表达与对照组之间，差异无显著性。结论：脐血中ＩＬ－１β和ＩＬ－１ｒα的表达可能与胎儿成熟度有关。     

免疫细胞因子在妊娠高血压综合征发病中的作用

目的 研究免疫细胞因子白细胞介素4（IL－4）、白细胞介素1β（IL－1β）、肿瘤坏死因子（TNF－α）在妊娠高血压综合征（简称妊高征）发病前后的变化，探讨免疫细胞因子在妊高征发病中的作用。方法 前瞻性研究550例孕妇，追踪到患有中、重度妊高征者25例（妊高征组），随意选30例正常健康孕妇作为对照组，分别取其孕12－16周和孕32－36周的血浆标本。用ELISA方法成批测定中孕期及晚孕期血浆中的IL－4、IL－1β、TNF－α水平。结果 （1）中孕期妊高征发病前血浆TNF-α水平，TNF-α/IL-4和IL－1β／IL－4比值均高于对照组（妊高征组分别为27.66ng/L,37.70,4.29；对照组分别为17.80ng/L,4.64,0.29）两组相比差异有显著性（P＜0.05）。（2）晚孕期妊高征发病后血浆TNF－α和IL－1β水平均高于对照组（妊高征组分别为52.49ng/L和29.46ng/L；对照组分别为35.51ng/L和7.93ng/L）两组比较差异有显著性（P＜0.05）。TNF-α/IL-4及IL－1β／IL－4比值两组间差异无显著性（妊高征组分别为12.3及6.98；对照组分别为23.8及11.79）。结论 妊高征发病前可能已存在着免疫细胞因子比例失衡，发病后细胞因子水平仍有明显变化，细胞因子免疫失衡可能与妊高征发病有关。     

妊高征患者白细胞介素6变化的意义

目的探讨妊高征患者白细胞介素６（ＩＬ６）变化的临床意义。方法用夹心酶联免疫法（ＥＬＩＳＡ）检测妊高征患者８２例（妊高征组）及正常妊娠妇女３０例（正常妊娠组）的血、尿中ＩＬ６的含量。结果重度妊高征患者血ＩＬ６含量较轻度妊高征患者和正常孕妇显著升高;妊高征组尿ＩＬ６含量均较正常妊娠组显著升高,且病情越重,升高越显著。妊高征组尿ＩＬ６与血肌酐（Ｓｃｒ）、内生肌酐清除率（Ｃｃｒ）分别成显著的正相关和显著的负相关关系,与尿β２微球蛋白（β２ＭＧ）、Ｎ乙酰βＤ葡萄糖苷酶（ＮＡＧ）分别成显著正相关。结论检测ＩＬ６有助于了解妊高征患者病情及其肾脏损害情况。     

妊娠高血压综合征患者血清白细胞介素-6水平分析

白细胞介素（ＩＬ）与异常的免疫激活及内皮细胞损伤的研究受到了重视〔１〕，为探讨白细胞介素－６（ＩＬ－６）与妊高征的关系，我们用ＥＬＩＳＡ方法测定了正常孕妇３５例和妊高征５３例血清的ＩＬ－６。现报告如下。１资料与方法１．１研究对象选择１９９４年１２月至...     

肿瘤坏死因子α白细胞介素1对体外培养的人子宫？…

目的 研究肿瘤坏死因子－α（ＴＮＦ－α）,白细胞介素－１（ＩＬ－１）对体外培养的人子宫内膜间质细胞生长的调节和对间质细胞泌乳素（ＰＲＬ）产生的影响,探讨ＴＮＦ－α,ＩＬ－１对女性生殖生理的调节作用。方法 ＭＴＴ比色法和放射免疫技术测定体外培养的人子宫膜间质细胞的增殖和ＰＲＬ的产生。结果 ＴＮＦ－α、ＩＬ－１均能抑制子宫内膜间质细胞的增殖及ＰＲＬ的产生,并随浓度增加抑制作用增强。结论 ＴＮＦ－α、Ｉ     

白细胞介素-6及其mRNA与妊高征发病的关系

目的 探讨白细胞介素－６（ＩＬ－６）及其ｍＲＮＡ与妊高征发病的关系。方法 应用逆转洋－聚合酶链反应（ＲＴ－ＰＣＲ）技术,检测５７例妊高征患者（妊高征组）及１５例正常妊娠妇女（正常妊娠组）母血白细胞及胎盘ＩＬ－６ｍＲＮＡ表达,同时采用酶联免疫吸附试验（ＥＬＡＳＡ）法检测母血及羊水中ＩＬ－６含量。结果（１）妊高征组母血ＩＬ－６及其ｍＲＮＡ含量随病中重呈升高趋势,与正常妊娠组比较,差异有极显著性,胎盘Ｉ     

两种细胞因子在早产儿和足月儿脐血中的表达

探讨产儿及足月儿出生时免疫功能的变化。采用细胞原杂交技术，对早产儿１６例和足月儿１８例出生时脐血的白细胞介素和白细胞介素－１受体拮抗剂基因表达水平进行分析。结果；观察组中，胎膜早破自娩的新生儿ＩＬ－１β 和ＩＬ－１ｒα的ｍＲＮＡ表达明显低于观察组中妊高征剖宫产新生儿和对照组。     

妊高征患者蜕膜组织中淋巴细胞转化率及细胞因子活性的变化

目的:研究妊娠高血压综合征(简称妊高征)的免疫学发病机制。方法:通过测定妊高征患者及正常孕妇蜕膜组织中淋巴细胞转化率,检测细胞培养液上清中白细胞介素-1(IL-1)、白细胞介素-2(IL-2)及肿瘤坏死因子α的活性,探讨妊高征的免疫学发病机制。结果:实验组淋巴细胞转化率、IL-1、IL-2、TNF-α活性均比对照组高,有显著统计学意义。且IL-2活性升高与淋巴细胞转化率存在明显的直线正相关。结论:蜕膜组织中的细胞因子异常升高及T细胞可能处于高免疫激活状态参与了妊高征的免疫学发病机制。     

妊高征患者外周血LGLs和TNF-α水平的测定

目的：探讨大颗粒淋巴细胞（ＬＧＬｓ）和肿瘤坏死因子－α（ＴＮＦ－α）与妊高征发病的关系。方法：应用双抗体夹心酶联免疫吸附法（ＥＬＩＳＡ）、全血细胞分析仪结合油镜下计数ＬＧＬｓ占淋巴细胞的百分数检测妊高征３９例（妊高征组），正常孕晚期４０例（正常妊娠组）和健康育龄非妊娠４０例（对照组）外周血ＴＮＦ－α含量和ＬＧＬｓ数量。结果：妊高征组外周血ＬＧＬｓ和ＴＮＦ－α水平高于正常妊娠组、对照组，以中、重度妊高征患者增高最为显著（Ｐ＜０．０５），其中合并胎儿宫内生长迟缓（ＩＵＧＲ）者外周血ＬＧＬｓ和ＴＮＦ－α水平与未合并ＩＵＧＲ者差异无显著性（Ｐ＞０．０５）。结论：细胞免疫，特别是ＬＧＬｓ和ＴＮＦ－α参与了妊高征的病理机制，妊高征发病与异常免疫激活有关     

Th1/Th2细胞因子在妊高征患者胎盘组织中的表达

目的 :探讨T辅助细胞 (Th) 1/Th2细胞因子在妊娠高血压综合征 (PIH)孕妇和血压正常的晚期妊娠妇女 (NLP)胎盘中的表达规律 ,从免疫学角度研究妊高征的发病原因及机制。方法 :选取PIH和NLP孕妇作为研究组和对照组 ,应用原位杂交法对两组胎盘的Th1型细胞因子 [肿瘤坏死因子 (TNF)α、白细胞介素 (IL) 2 ]和Th2型细胞因子 (IL 10 )进行标记并通过彩色病理图像分析系统对染色结果进行定量检测并作比较。结果 :(1)TNFαmRNA、IL 2mRNA在PIH及NLP组胎盘合体滋养细胞表达的平均光密度分别为0 .1978± 0 .0 32 1、0 .2 0 39± 0 .0 4 11及 0 .16 79± 0 .0 30 9、0 .16 0 0± 0 .0 4 46 (P <0 .0 0 1) ,随着PIH病情加重 ,表达逐渐增强 (P <0 .0 5 ) ;(2 )IL 10mRNA在PIH及NLP组胎盘合体滋养细胞表达的平均光密度分别为 0 .15 6 4± 0 .0 4 36及 0 .2 0 17± 0 .0 32 1(P <0 .0 0 1) ,随着PIH病情加重 ,表达逐渐减弱 (P <0 .0 5 )。结论 :在妊高征孕妇胎盘中表现为免疫杀伤的Th1型细胞因子表达增强 ,与病情呈正相关。表现为免疫保护或免疫营养的Th2型细胞因子则表达减弱 ,与病情呈负相关。提示母胎界面的Th1/Th2细胞因子平衡偏离可能是导致PIH发病的病因之一。     

TNFα、IL-4及IL-10在妊高征孕妇胎盘中的表达

目的:研究肿瘤坏死因子α(TNFα)、白细胞介素(IL)-4及IL-10在妊高征(PIH)孕妇胎盘中的表达规律,探讨它们与妊高征发病的关系。方法:用原位杂交法对TNFαmRNA、IL-4mRNA及 IL-10mRNA在54例 PIH孕妇和32例正常血压的晚期妊娠(NLP)孕妇胎盘的表达进行检测。结果:TNFαmRNA、IL-4mRNA及IL-10mRNA在两组均主要表达于胎盘的合体滋养细胞浆,经图像分析处理:①TNFαmRNA在PIH及NLP组的平均光密度分别为0.1947±0.0303及0.1681±0.028　8(P　<0.001)。②　PIH组的IL-4mRNA、IL-10mRNA平均光密度分别为0.1478 ±0.0468、0.1585±0.0402,均低于NLP组(0.2081±0.0280、0.2019±0.0289),P　<0.001。结论:孕妇母-胎界面的TNFαmRNA表达升高、IL-4mRNA及IL-10mRNA表达降低导致的免疫失衡可能是PIH的病因之一。     

VCAM-1和IL-6在妊娠高血压综合征发病中的作用

目的:探讨妊娠高血压综合征(妊高征)患者血清中血管细胞粘附分子-1(VCAM-1)和白细胞介素-6(IL-6)水平的变化,及其在妊高征发病中的作用。方法:采用双抗体夹心酶联免疫吸附法(ELISA)测定了49例妊高征患者(其中轻度15例、中度16例及重度18例),35例正常晚期妊娠妇女的血清VCAM-1和IL-6含量。结果:(1)妊高征组血清VCAM-1和IL-6浓度都明显高于正常妊娠组(P<0.05,P<0.01);(2)VCAM-1与IL-6水平呈明显正相关。结论:血清中VCAM-1和IL-6含量的升高可能参与了妊高征血管内皮细胞损伤过程,IL-6可以诱导VCAM-1的表达,2者共同参与了妊高征的发病过程。     

妊娠高血压综合征患者蜕膜组织中免疫相关细胞变化的研究

目的研究妊高征的免疫学发病机制。方法通过对妊高征患者及正常孕妇胎盘蜕膜组织中免疫相关细胞进行光镜观察,测定淋巴细胞转化率,探讨蜕膜免疫相关细胞的变化与妊高征之间的关系。结果蜕膜中大颗粒淋巴细胞及凋亡细胞显著增多,ＣＤ＋５７细胞数量及ＣＤ＋４与ＣＤ＋８比例上升,淋巴细胞转化率明显升高。结论蜕膜中免疫相关细胞参与了妊高征的免疫学发病机制。     

Programming of human monocytes by the uteroplacental environment

During human pregnancy, monocytes recruited to the uterus (decidua) are modified to promote immune defense and semiallogeneic pregnancy. The purpose of this study was to identify decidual factors involved in programming of monocytes into decidual macrophages by comparing the surface and secretory phenotypes of resting and interferon- gamma (IFN-gamma)-activated monocytes, unfractionated decidual cells, purified term decidual macrophages, and monocyte-derived macrophages. Surface markers for antigen presentation (HLA-DR, CD86), a membrane-bound cytokine interleukin (IL)-15, leukocyte immunoglobulin-like receptors (LILRB1, LILRB2), and secreted anti-inflammatory cytokines (transforming growth factor [TGF]-beta1 and IL-10) were assessed. The results demonstrate that differentiated, activated monocytes closely resemble but are not identical to decidual macrophages. In addition to differential IFN-gamma responsiveness, decidual macrophages were smaller than monocyte-derived macrophages and produced IL-10, which monocyte-derived macrophages did not. Only the unfractionated decidual cells secreted TGF-beta1. These results suggest that activation, differentiation, and decidual signals cooperate to program monocytes into the decidual macrophage phenotype.     

Exogenous Soluble VEGF Receptor-1 (sFlt-1) Regulates Th1/Th2 Cytokine Production from Normal Placental Explants via Intracellular Calcium

Objective: The increase of soluble VEGF-Receptor 1 (sFlt-1) is thought to contribute to the pathogenesis of preeclampsia. Soluble VEGF-Receptor 1 binds to circulating free VEGF and PLGF and this cascade is associated with endothelial dysfunction, a prominent feature of preeclampsia. Preeclampsia is also associated with excessive maternal response to pro-inflammatory stimuli manifesting as an imbalance of Th1/Th2 cytokine production at the maternal-fetal interface. Whether increased sFlt-1 expression has any effect on placental production of Th1/Th2 cytokines IL-10 and TNF-α is yet to be investigated. The aim of this study is to examine if exogenous sFlt-1 can regulate Th1/Th2 cytokines IL-10 and TNF-α production from normal placental explants via intracellular calcium release.?Methods: Placental explants were taken from the decidual surface of normal non-laboured term placentas (n = 11).Villous explants were cultured with increasing concentrations of sFlt-1. The dose effect of sFlt-1 on placental Th1 and Th2 cytokine production (TNF-α and IL-10) were examined. Free PLGF, VEGF and sFlt-1 concentrations in the conditioned medium were also measured. Intracellular calcium blocker, 1,2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid, tetra(acetoxymethyl)-ester (BAPTA/AM) was applied to investigate whether the changes in cytokine concentration were mediated by intracellular free calcium.?Results: Placental IL-10 and TNF-α production were significantly increased after sFlt-1 incubation. The increase in IL-10 can be inhibited by BAPTA/AM. Soluble Flt-1 and free PLGF concentration in the conditioned medium was not changed. Free VEGF concentration in the conditioned medium was not detectable.?Conclusion: Exogenous sFlt-1 can increase TNF-α and IL-10 production from normal placental explants. The change in Th1/Th2 cytokine level may be mediated by intracellular free calcium.     

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.     

外源性细胞因子对早孕蜕膜T细胞免疫活性的研究

目的 :探讨外源性细胞因子对早孕蜕膜T细胞免疫活性作用的方式。方法 :在培养的蜕膜细胞中加入γ干扰素、白细胞介素 2、白细胞介素 6和表皮生长因子 ,共同培养 12、2 4、4 8h后收集上清液 ,并加入培养的T细胞中 ,用氚 胸苷 (3 H TdR)掺入法测定T细胞的转化值。结果 :在蜕膜与细胞因子共同培养的上清液作用下 ,各实验组T细胞的转化有不同程度的升高 ,有的T细胞转化效应显著增强 (P <0 .0 5 ) ,但增强的T细胞转化效应未显示出与作用于蜕膜的细胞因子种类、浓度及作用时间有相关性。结论 :在外源性细胞因子的作用下 ,早孕蜕膜细胞可以增强T细胞的转化作用 ,从而破坏蜕膜免疫微环境细胞因子网络的平衡状态 ,危害妊娠。