足月妊娠产妇羊水中IL-6,IFN-γ,IL-8,GM-CSF的浓度

细胞因子有助于成功地维持妊娠,并与启动分娩有关。IL-6能刺激羊膜及蜕膜产生PGE_2,与正常分娩的生理学有关;IL-8与子宫颈的成熟过程有关,有报道证实在分娩过程中子宫下段IL-8产生增多。在人妊娠过程中,胎盘合体滋养层产生IFN-γ,蜕膜及滋养层产生GM-CSF。这些细胞因子的部分功能与胎盘的生长及分化有关,但它们对分娩机制的作用尚不清楚。为确定可能与足月妊娠分娩机制有关的细胞因子,检测母体外周血,子宫静脉血,脐动脉血,羊水中IL-6,IFN-γ,IL-8及GM-CSF的浓度。方法:实验组10例标本为顺产妇(6例羊膜未破,4例羊膜破裂<6h);对照组标本为剖宫产产妇。分别取外周血,子宫静脉血,脐动脉血及羊水,应用ELISA     

Different levels of IL-1α, IL-6, TNF-α, NF-κB and PPAR-γ in monocyte cultures exposed by plasma preeclampsia and normotensive pregnancy

ObjectiveTo determine different levels of proinflammatory cytokines IL-1α, IL-6, TNF-α, nuclear NF-κB p50 and PPAR-γ in monocyte cultures exposed to normotensive pregnancy plasma compared with those exposed to preeclamptic plasma.Study designThe study involved primigravidae with preeclampsia (12) and normotensive pregnancy (12) in which their blood plasma was given to monocyte cultures from isolated PBMC of healthy and non-pregnant women. They were divided into 2 groups, the first group was incubated for 24 h and the second one was incubated for 48 h (step 1). The levels of IL-1α, IL-6, TNF-α, and nuclear NF-κB p50 as well as PPAR-γ of both groups were subsequently measured and compared (step 2). Data were analyzed to determine the differences and interaction between both treatment groups using one-way ANOVA.ResultsThere was a significantly different level (p-value <0.05) of IL-1α in monocyte cultures incubated for 24 h compared with those incubated for 48 h, as shown in step 1 of the study. Meanwhile, step 2 of the study found significantly different levels of IL-1α, IL-6, TNF-α, and NF-κB p50 in monocyte cultures exposed to preeclamptic plasma compared with those exposed to normotensive pregnancy, in which the latter showed higher levels. Both groups also showed decreased levels of PPARγ, in which monocyte culture exposed to severe preeclamptic plasma (p value <0.05).ConclusionPreeclamptic plasma significantly increased levels of proinflammatory cytokines IL-1a, IL-6, and TNF-a in monocyte cultures. This condition was consistent with the increasing of NF-κB p50 and decreasing of PPARγ.     

Plasma IL-4, IL-8, IL-12, interferon-γ and CRP levels in pregnant women with preeclampsia,and their relation with severity of disease and fetal birth weight

Objective: The aim of the present study was to evaluate the hypothesis that preeclampsia is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses compared with normal pregnancy. We also sought to determine whether there was a correlation between these markers with severity of preeclampsia and fetal birth weight. Methods: The study population consisted of maternal age, gestational age, and body mass index matched 138 pregnant women; 56 normotensive healthy pregnant women (group 1), 42 women with mild preeclampsia (group 2), 40 women with severe preeclampsia (group 3). Results: Plasma interleukin (IL)-8 and C-reactive protein (CRP) levels were significantly higher in group 3 than group 1 (p?<?0.05). Plasma IL-4, IL-12, and interferon (IFN)-γ levels were similar in all groups. Although plasma IL-8 and CRP levels of mild preeclamptic group were higher than control group and lower than severe preeclamptic group, the differences were not statistically significant. There was a positive correlation between IL-12 and fetal birth weight in severe preeclamptic group (p?<?0.05). Conclusions: Elevated maternal serum pro-inflammatory cytokine IL-8 and CRP in severe preeclamptic women compared with normal pregnant women supports the hypothesis that preeclampsia is associated with increased inflammatory responses.     

IL-1β up-regulates expression of IL-8 in endometrial stromal cells in vitro

Endometriosis(EMs),which presents a majorchallenge to gynecologist,is a common disease amongreproductive-aged women and its morbidity increases inrecent years.Besides genetic,hormonal,and environ-mental factors involved in the development,many stud-ies on endometriosis indicate that there are more cellsrelevant to the immunoinflammatory process and vari-ous cytokines infiltrating into ectopic and eutopic endo-metrium of endometriosis than into endometrium ofhealthy women[1].IL-1β,one of the …     

IL-1ra对IL-1β诱导子宫内膜异位症在位内膜基质细胞分泌RANTES的拮抗作用研究

目的 :研究IL -1受体拮抗剂 (IL -1ra)对IL- 1β介导的细胞生物学功能的影响 ,为基因工程药物IL- 1ra用于妇产科临床提供理论依据。方法 :取培养 3～ 5代的子宫内膜异位症的基质细胞分别加入不同浓度的IL -1β与IL- 1ra ,用ELISA双抗体夹心法测定细胞培养上清液中RANTE的含量。结果 :IL -1β作用后 ,EMs在位内膜基质细胞培养上清液中的RANTES含量明显增高 (P <0 .0 1)。当用一定浓度的IL 1ra封闭IL -1受体后加用IL -1β ,细胞培养上清液中RANTES含量呈降低趋势 ,结果有统计学意义 (P <0 .0 5 )。 结论 :IL- 1ra有拮抗IL- 1β诱导EMs在位内膜基质细胞分泌RANTES的作用。     

羊膜、绒毛膜的炎性细胞因子(IL-1β和IL-6)表达

在胎膜早破或早产者中,羊膜感染或羊膜亚临床感染发病率很高。这些孕妇羊水中有高水平的炎性细胞因子——白细胞介素1β(IL-1β),白细胞介素6(IL-6),肿瘤坏死因子α(TNF-α)。为确定羊膜、绒毛膜产生IL-1β和IL-6的基本状况,以及对内毒素刺激的反应。采用如下方法:①羊膜、绒毛膜取自足月择期剖宫产者和羊膜有感染史、羊水细菌培养阳性者。所取标本洗净血污后,分别切成5mm和9mm直径的组织块作培养。②培养后组织经液氮冷冻后,提取mRNA,用逆转求PCR(RT-PCR)方法扩增,然后电泳观察结果。③培养后组织用4％多聚甲醛固定后切片,用生物素标记寡核苷酸探针作原位杂交,定位mRNA;用鼠抗人IL-1β和IL-6单克隆抗体、生物素标记二抗、酶标抗生物素蛋白作免疫组化,检     

Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia,and their relation with severity of disease

Abstract

Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants.

Methods: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version.

Results: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p?<?0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p?<?0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age.

Conclusions: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.     

细菌性阴道病和早产者宫颈分泌物IL-1βIL-6含量变化的相关性

目的　探讨宫颈分泌物细胞因子 (IL - 1β和IL - 6 )含量与细菌性阴道病 (BV)、早产的关系。 方法　选择孕 32～ 34周无宫缩而胎膜完整的有BV孕妇 2 7例和无BV孕妇 30例 ,以及胎膜完整的未足月临产孕妇 2 5例和足月临产孕妇 2 6例 ,进行宫颈分泌物取样 ,分别采用酶联免疫吸附法和放射免疫法测定宫颈分泌物IL -1β、IL - 6的含量。 结果　宫颈分泌物IL - 1β的含量在BV组和未足月临产组均高于无BV组 (P <0 0 5 ) ,而未足月临产组与足月临产组间无差异 (P >0 0 5 ) ;宫颈分泌物IL - 6的含量各组相比均无显著性差异 (P >0 0 5 )。结论　宫颈分泌物IL - 1β含量的升高与BV及早产有关 ,可能在BV引起的早产中起一定的作用     

IL-1β predicts IVF outcome: a prospective study

Purpose

Retrospective cohort studies have shown a relationship between maternal serum interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) levels and in vitro fertilization (IVF) cycle outcome. The objective of this investigation was to explore the correlation between serum IL-1β and/or IL-1Ra levels obtained prospectively and IVF outcomes.

Methods

Sera from 205 women were collected just prior to initiation of their IVF cycle, at the time of human chorionic gonadotropin administration, day 24 of IVF cycle, day 28, and day 35. Sera were analyzed for IL-1β and IL-1Ra using commercially available ELISA kits. Cycle outcomes were followed prospectively. Data were analyzed using Friedman analysis of variance by ranks and chi-square analysis.

Results

Among women with a viable pregnancy, IL-1β serum levels increased over time for those that proceeded to deliver or had an ongoing pregnancy. There was no increase in serum levels for those with subsequent pregnancy loss. Of the women that had an embryo transfer, detectable IL-1β levels at the start of the cycle were associated with successful IVF outcome (p =?0.027). Of women with a positive pregnancy test, undetectable IL-1β at the start of the cycle were associated with subsequent pregnancy loss (p =?0.046). For all IL1-Ra serum analysis, there were no significant results.

Conclusions

The increasing levels of IL-1β over time are consistent with the known role of the IL-1 cytokine family in implantation and pregnancy. Additionally, we confirm in a prospective investigation the positive relationship between detectable serum IL-1β at the start of IVF cycle and outcome.

     

IL-1系统与胚泡着床的关系

<正>胚泡着床是成功妊娠的第一步,但其精确机制还不清楚.遗传学和分子生物学技术发展为着床的研究提供了新的手段.近年,人们从胚泡着床的分子机制方面进行了探索,细胞因子是一个引人注目的领域,其在着床中的作用日渐受到重视,其中白介素一1(Interleukin-l,IL-1)系统对胚泡着床的影响较大,研究资料较多,本文就近几年的文献作一综述.     

胎儿血清及含有胎粪的羊水中IL-1β和IL-6的不同表达

胎粪是胎儿胃肠道的产物,妊壤10～16周时在回肠出现。胎粪的出现可能与妊娠期间胎儿-胎盘单位的完整性,胎-母状态有关。羊水中含有胎粪将增加胎-母危险性,特别是胎儿暴露和羊水浓缩时。与相应对照组相比,早期羊水中即出现稀薄胎粪的胎儿,其发生胎粪相关综合征及其他疾病的发病率高。且常将出现胎粪视作产前或分娩中胎儿窒息的指标。羊水中含有胎粪很常见,其机制和原因尚不     

溶脲脲原体对体外培养大鼠支持细胞分泌IL-1α和IL-6的影响

目的 :研究溶脲脲原体 ( ureaplasma urealyticum,UU)对大鼠睾丸支持细胞分泌 IL- 1 α和 IL- 6的影响。方法 :2 0 d龄雄 SD大鼠 8只 ,无菌取睾丸 ,经 型胶原酶和透明质酸酶消化 ,分离出纯度较高的支持细胞 ,用 DMEM/Ham's F- 1 2培养液培养。实验组加入 UU一起培养 ,对照组则加 UU培养基。分别取培养 1～ 4d的细胞上清液 ,用 ELISA法检测其 IL- 1α和 IL- 6的含量。结果 :实验组与对照组相比 ,IL- 1α的含量显著降低 ( P<0 .0 1 ) ,IL- 6的含量显著升高 ( P<0 .0 1 )。结论 :UU感染使支持细胞分泌 IL- 1 α减少 ,却明显促进 IL- 6的分泌。提示 UU感染与生殖道 (腺 )局部免疫有关     

细胞因子(IL-1β、IL-6、TNF-α)在早产宫内感染中的价值

目的 探讨与感染有关的细胞因子(interleukin-1β,IL-1β)、(interleukin-6,IL-6)、(tumor necrosis factor-a,TNF-α)在早产中的应用.方法 取30例早产孕妇和31例足月临产孕妇,46例足月未临产孕妇的血和羊水标本,分别行血IL-6、羊水中IL-1β、IL-6及TNF-α和胎盘行病理检查.结果 (1)早产组的羊水中IL-1β、IL-6、TNF-α及血浆中IL-6水平显著高于妊娠足月组(包括临产组和未临产组).早产组中有宫内感染孕妇的细胞因子水平显著高于无宫内感染者.(2)羊水和血浆中IL-6水平有明显的相关性.结论 早产有宫内感染者血浆及羊水中细胞因子水平高于无宫内感染者,血浆IL-6水平与羊水IL-6水平密切相关.     

Expression of lipoxin A4, TNFα and IL-1β in maternal peripheral blood,umbilical cord blood and placenta,and their significance in pre-eclampsia

Objective: The purpose of this study was to investigate the expression of lipoxin A₄, TNFα and IL-1β in maternal peripheral blood, umbilical cord blood and placenta, and to assess their significance in pre-eclampsia. Methods: Ninty pregnant women were divided into three groups: a mild PE group (n?=?30), a severe PE group (n?=?30) and a control group (n?=?30). We measured serum levels of lipoxin A₄, TNFα and IL-1β using ELISA. Expression levels of lipoxin receptor (FPR2/ALX) mRNA were compared using quantitative RT-PCR. Results: Mean circulating levels of lipoxin A₄, TNFα and IL-1β in the PE groups were significantly increased compared with matched women in the control group. The ratios of lipoxin A₄/TNFα and of lipoxin A₄/IL-1β in the PE groups were significantly decreased compared with matched women in the control group. No lipoxin A₄ was detected in umbilical cord blood. There was a significant increase in FPR2/ALX mRNA expression in placenta obtained from the PE groups. Conclusions: The level of lipoxin A₄ in maternal peripheral blood may correlate with the expression of FPR2/ALX in placenta. Lipoxin A₄ increased to a lesser degree than either TNFα or IL-1β with progression of PE. This may be one of the reasons why oxidative stress and endothelial dysfunction in severe preeclamptic patients are much more serious that in cases of less severe preeclampsia. Moreover, lipoxin A₄ does not have any effect on the fetus through the placenta. We conclude that supplementing with lipoxin A₄ to ensure adequate levels may be a novel method for the treatment of pre-eclampsia without any effects on the fetus.     

人妊娠血清对IL-1合成及其效应的抑制作用

已报道妊娠血清(PS)可非特异性地抑制对有丝分裂原的应答性及混合淋巴细胞反应(MLR)。MLR 中 T 细胞激活需有白细胞介素1(IL-1)及同种异体抗原。这二种刺激同时诱导 T_H 细胞合成白细胞介素2(IL-2),并诱导 IL-2受体阳性细胞进入 S 期。也已证实 PS 可抑制 T_H 增殖及 MLR 中IL-2合成。本文旨在分析 PS 对 IL-1的“抑制作用”,是通过影响其合成抑或是通过抑制其特异性活性所致。作者自孕龄8周的初次或多次妊娠孕妇收集血清,以男性供者血清即正常人血清(NHS)作为正常对照。以正常供者的外周血单核细胞(PBMC)作单向 MLR。将人 PBMC 加脂多糖(LPS)刺激,分别加入 PS 和 NHS,37℃培养24小时。收     

IL-1β and IL-23 in amniotic fluids of ultrasound-detected aortic intima/media thickness and growth retardation

Intrauterine growth restriction (IUGR) and/or neonatal low birth weight are often associated with increased intima/media thickness of the abdominal aortic wall (aIMT). Several studies in children suggested that aIMT might be related to inflammation, probably indicating an early stage of adulthood diseases, such as atherosclerosis. Our previous study performed on the abdominal aortic wall of a stillbirth presenting with IUGR and aIMT suggested an association among IUGR, aIMT, and inflammation, also highlighting the presence of fibroblastoid cells, which are thought to represent peculiar elements of the pre-atherosclerotic lesions. These observations led us to analyze two cytokines involved in the inflammation cascade, IL-1β and IL-23, in amniotic fluid samples of IUGR fetuses and small-for-gestational-age newborns presenting with aIMT and in normal controls. Our results indicate that IL-23, but not IL-1β, concentrations differed in the groups analyzed. Therefore, IL-23, a regulatory element that bridges the innate and adaptive arms of the immune system, might be involved in the inflammatory process observed in fetal aIMT.     

母乳巨噬细胞产生及分泌IL-1的功能不全

单核吞噬细胞具有功能上的异质性,其产生IL-1(白细胞介素1)的能力随细胞群的不同而异。母乳巨噬细胞(HMMφ)是乳汁中的主要细胞群,具有吞噬及抗原递呈功能,但产生IL-1的功能尚未证实。本文作者就此进行研究。选择49例16～41岁健康母亲,在产后72h取血及乳汁标本。经Ficoll-Hypaque密度梯度离心,分离出其中的单核细胞,分别配成1×10~6/ml的HMMφ及1×10~6/ml的血单核细胞(HMo)悬液,染料排除试验证实二者活性均>95%。分别在HMo及HMMφ培养中加入40μg脂多糖(LPS),另有二组不加LPS,培养24h后,测上清中IL-1的活性,表明绝大多数HMMφ受刺激后不生成可测的IL-1,而来自同一供体的HMo则能产生高水平的IL-1。进一步测定该状态下细胞内IL-1的活性,发现多数情况下,未受刺激的HMMφ胞内IL-1活性低于可测水平限度;但受LPS刺激后,胞内IL-1活性增至19±12U/ml,与受刺激后的