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，ＣＤ５７＾＋细胞数量及ＣＤ４＾＋与ＣＤ８＾＋比例上升，淋巴细胞转化率明显升高。结论 蜕膜中免疫细胞参与了妊高片的免疫学发病机制。     

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。     

妊娠高血压综合征免疫学发病机制的研究

目的：研究妊娠高血压综合征（妊高征）的免疫学发病机制。方法：通过检测妊高征患者及正常孕妇蜕膜组织细胞培养上清液中白细胞介素－１（ＩＬ－１）、白细胞介素－２（ＩＬ－２）和肿瘤坏死因子－α（ＴＮＦ－α）的活性，分析蜕膜免疫细胞因子的变化与妊高征之间的关系。结果：与正常孕妇相比，妊高征患者蜕膜组织中ＩＬ－１、ＩＬ－２和ＴＮＦ－α的分泌显著升高。结论：蜕膜组织免疫微环境中细胞因子的改变可能是妊高征发病的机制之一     

妊高征孕妇外周血NK细胞及单核细胞白细胞介素6、白细胞介素8含量的测定

近年来的研究提示免疫失衡与妊高征的发病有关。杀伤细胞 (NK细胞 )可能参与妊高征的发病过程。本研究测定妊高征患者外周血 NK细胞的活性、比例及白细胞介素 6 (IL- 6 )、白细胞介素 8(IL- 8)含量 ,以探讨妊高征发病与 NK细胞的关系。　　作者单位 :610 0 61　成都 ,解放军四五二医院妇产科 (李文 ) ;第三军医大学大坪医院妇产科 (陈竹钦 ) ;西南医院免疫实验室 (黄兴玉 )　　一、资料与方法1.对象 :选择 1995年 1月～ 1995年 12月在第三军医大学西南医院、新桥医院以及大坪医院住院的妊高征患者 2 6例 ,正常晚孕妇女 2 2例 ,女性健康…     

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。     

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。     

妊高征患者纤溶酶原激活物抑制剂1型,凝血酶抗凝血酶Ⅲ复合物及D双聚体的变化

目的 测定妊高征患者中的凝固-纤溶因子的变化,探讨胎盘局部凝固-纤溶系统的调节及其在妊高征发病机制中的作用.方法 用放射免疫法测定重度妊高征及正常孕妇的羊水、母体血浆及胎盘组织中纤溶酶原激活物抑制剂1型(PAI-1)、凝血酶抗凝血酶Ⅲ复合物(TAT)及D双聚体(D-dimer)的含量,用人胎盘蜕膜细胞培养系统进行凝血酶负荷试验.结果 在正常妊娠的PAI-1、TAT在羊水中含量分别为(809.2±79.8),(872±214) ng/ml,明显高于母体血浆的(140.9±38.3),(6.1±0.4)ng/ml,胎盘组织中PAI-1含量,蜕膜组织(415.7±39)ng/mg明显高于绒毛组织(93.9±10)ng/mg.在妊高征患者,羊水及胎盘蜕膜组织PAI-1分别为(1 474.5±254.7) ng/ml及(1 164±132) ng/mg蛋白、TAT(132±253.1) ng/ml,D-dimer(132±27.8)ng/ml显著高于正常妊娠.凝血酶可刺激胎盘蜕膜细胞增加PAI-1的产生和分泌,两者存在着量效关系.结论 妊高征中胎盘蜕膜细胞产生和分泌PAI-1水平的增加,使胎盘凝固-纤溶系统发生改变,即凝固亢进,纤溶活性降低.这些改变可能与妊高征发病机制有关.     

妊高征患者胎盘组织中FasL的表达及其意义

目的　探讨FasL在妊高征患者胎盘组织中的表达是否异常 ,进一步从免疫学角度分析妊高征的发病机制。方法　 2 0 0 1年 11月至 2 0 0 2年 7月 ,采用免疫组织化学SP法检测 2 0例正常孕妇 (对照组 ) ,6 5例妊高征患者 (妊高征组 ,其中轻度 2 2例、中度 2 0例、重度 2 3例 )胎盘组织中FasL表达强度。结果　FasL主要表达于胎盘绒毛滋养细胞 ,妊高征组胎盘绒毛滋养细胞及蜕膜组织细胞FasL表达强度明显低于对照组 (P <0 0 1,P <0 0 5 )。结论　妊高征患者胎盘组织FasL表达减少 ,母胎免疫耐受机制遭到破坏 ,引发胎盘绒毛发育不全、功能下降等一系列免疫病理改变 ,最终可能导致妊高征及其并发症的发生。     

可溶性细胞粘附分子1、促肾上腺皮质激素释放激素及白细胞介素6在妊娠高血压综合征发病中的作用

目的　研究可溶性细胞粘附分子 1(soluble intracellular adhesion m olecule- 1,s ICAM-1)、促肾上腺皮质激素释放激素 (cortictropin- releasing horm one,CRH)及白细胞介素 6 (interleukin-6 ,IL- 6 )在妊娠高血压综合征 (妊高征 )发病中的作用。　方法　测定 81例妊娠 2 6～ 37周孕妇血浆s ICAM- 1、CRH、IL- 6水平 ,其中 2 3例 ,为正常孕妇 (正常妊娠组 ) ;5 8例为妊高征孕妇 (妊高征组 ) :包括轻度 2 1例、中度 19例、重度 18例。用酶联免疫法测定 s ICAM- 1及 IL- 6 ,用放射免疫法测定 CRH。　结果　中、重度妊高征患者的血 s ICAM- 1、CRH、IL- 6水平均显著高于正常对照组 (P<0 .0 5 ) ,轻度妊高征患者与正常组相比虽无统计学差异但有升高的趋势。IL- 6水平与 CRH呈正相关 (r=0 .5 1,P<0 .0 5 )。　结论　妊高征患者血 s ICAM- 1升高表明内皮细胞损伤在妊高征的发病中起重要作用。CRH分泌的异常增加可能与内皮细胞的损伤有关 ,该作用可能是通过促进 IL- 6的分泌实现的     

Fas/FasL系统表达异常与妊娠高血压综合征的关系

近年来，免疫因素在妊娠高血压综合征(妊高征)发病机制中的作用越来越受到人们的重视。国外研究发现，Fas/FasL系统在正常母．胎免疫耐受中起重要作用。本研究旨在对妊高征及正常孕妇的血清可溶性Fas(sFas)及胎盘绒毛滋养细胞和蜕膜组织细胞中的Fas／FasL表达进行研究，进一步从分子免疫学角度探讨妊高征发病机制。     

The effects of hypoxia and hyperoxia on fetal-placental vascular tone and inflammatory cytokine production.

OBJECTIVE: To determine the effects of fetal hypoxia and hyperoxia on placental vascular tone and production of interleukin-6 and tumor necrosis factor-alpha. STUDY DESIGN: The maternal and fetal circulation of 2 cotyledons from 5 human placentas were perfused for 4 hours. The fetal circulation of 1 cotyledon was perfused with hypoxic Hanks' balanced salt solution; the other was perfused with hyperoxic Hanks' balanced salt solution. Fetal vascular pressures were recorded every 10 minutes, and fetal vein effluents were collected hourly. RESULTS: Fetal-placental vascular perfusion pressure was reduced from baseline during hypoxic conditions. Cytokine concentrations were elevated during hyperoxic conditions compared with hypoxic conditions, with significant differences achieved at 2, 3, and 4 hours for interleukin-6 and at 4 hours for tumor necrosis factor-alpha. CONCLUSION: Fetal-placental vasodilation may be a compensatory mechanism to improve hypoxic conditions. Supraphysiologic oxygenation may contribute to the fetal inflammatory response syndrome and to the development of cerebral palsy.     

Transforming growth factor-beta opposes the stimulatory effects of interleukin-1 and tumor necrosis factor on amnion cell prostaglandin E2 production: implication for preterm labor.

OBJECTIVE: In preterm labor increased concentrations of interleukin-1 and tumor necrosis factor are present in amniotic fluid. These cytokines may promote labor by stimulating the production of prostaglandins by intrauterine tissues. In many biologic processes, transforming growth factor-beta modifies the actions of cytokines. We studied the effect of transforming growth factor-beta on the cytokine-induced prostaglandin E2 production by amnion cells. STUDY DESIGN: Human amnion cells in monolayer culture were treated with interleukin-1, tumor necrosis factor, or vehicle in the presence or absence of transforming growth factor-beta. The prostaglandin E2 production was measured. RESULTS: Transforming growth factor-beta decreased the interleukin-1- or tumor necrosis factor-induced prostaglandin E2 production by 70% to 80% and the basal prostaglandin E2 synthesis by 27%. The synergistic stimulation of prostaglandin E2 production by the combination of interleukin-1 with tumor necrosis factor was inhibited by 80% in cells treated with transforming growth factor-beta. Transforming growth factor-beta 1, -beta 2, and -beta 1,2 were equipotent. CONCLUSION: Transforming growth factor-beta suppresses the cytokine-induced prostaglandin E2 production by amnion cells and may be an important factor in maintaining pregnancy in the face of labor-promoting cytokines.     

Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles

OBJECTIVE: To investigate the serum and intrafollicular tumor necrosis factor-alpha and interleukin-6 concentrations in infertile women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). METHODS: Thirty-one patients with PCOS undergoing IVF were studied. Thirty-nine normally ovulating women matched for age and body mass index and undergoing IVF for male infertility were the control group. Serum tumor necrosis factor-alpha, interleukin-6, and estradiol levels were assayed before recombinant follicle-stimulating hormone stimulation under gonadotropin-releasing hormone analogue suppression and 34-36 hours after human chorionic gonadotropin (hCG) administration at the time of the oocyte retrieval. Cytokine and estradiol concentrations were also evaluated in the follicular fluids obtained at the time of oocyte retrieval. RESULTS: The patients with PCOS had higher serum and follicular fluid tumor necrosis factor-alpha and interleukin-6 concentrations (P <.001) and lower follicular fluid estradiol levels (P <.05) than control women. In both groups, the serum tumor necrosis factor-alpha, interleukin-6, and estradiol values increased significantly after hCG stimulation. In both groups, the follicular fluid cytokine concentrations were higher than those found in the serum. In the PCOS women the follicular fluid tumor necrosis factor-alpha values were significantly and inversely correlated to the follicular fluid estradiol values (rho = -0.79; P <.001); this correlation was not found in the control subjects. CONCLUSION: In infertile women with PCOS, 1). serum and follicular fluid interleukin-6 and tumor necrosis factor-alpha values were higher than those found in control women, 2). the cytokine concentrations were higher in the follicular fluid than in the serum, and 3). the intrafollicular tumor necrosis factor-alpha concentrations were significantly and inversely correlated to the estradiol levels. These results suggest an involvement of the immune system in PCOS.     

Endotoxin-induced cytokine production of monocytes of third-trimester pregnant women compared with women in the follicular phase of the menstrual cycle

OBJECTIVE: Little is known about the function of the innate immune response during pregnancy. We therefore investigated monocyte cytokine production, as a measure of monocyte function, in pregnant women compared with nonpregnant women. STUDY DESIGN: Whole blood of women in the follicular phase (day 5-6) and of healthy pregnant women (30 weeks) was collected and stimulated with endotoxin (2 microg/mL). After incubation for 4 hours (37 degrees C, 5% carbon dioxide), red blood cells were lysed and white blood cells were permeabilized, followed by staining with anti-CD14 (fluorescein isothiocyanate labeled) and with phycoerythrin-labeled tumor necrosis factor-alpha, interleukin-1beta, or interleukin-12. The cells were analyzed by flow cytometry after fixation. Results are expressed as a percentage cytokine producing cells after endotoxin stimulation. Statistical analysis was performed with the Mann-Whitney U test (P <.05). RESULTS: Compared with the percentage endotoxin-induced cytokine producing peripheral monocytes in women in the follicular phase, this percentage in pregnancy was decreased for interleukin-12 (mean 6.63 +/- 1.34 vs 3.34 +/- 0.87, P <.05) and tumor necrosis factor-alpha (mean 50.20 +/- 5.80 vs 31.29 +/- 5.57, P >.05). No significant difference was seen in the production of interleukin-1beta (mean 58.22 +/- 11.09 vs 47.18 +/- 7.88, P >.05). CONCLUSION: The percentage of interleukin-12 and tumor necrosis factor-alpha producing monocytes is decreased in pregnant women compared with nonpregnant women, suggesting that pregnancy is a proinflammatory state.     

Increased tumor necrosis factor-alpha production after lipopolysaccharide stimulation of whole blood in patients with previous preterm delivery complicated by intra-amniotic infection or inflammation.

OBJECTIVE: To compare cytokine production after lipopolysaccharide stimulation of whole blood from women who were delivered of infants at term compared with women who were delivered of preterm infants with intra-amniotic evidence of infection or inflammation. STUDY DESIGN: Whole blood samples from 12 women who were not pregnant and who had previously had preterm deliveries before 32 weeks complicated by intra-amniotic infection or inflammation and samples from 12 age- and race-matched control subjects were stimulated with Escherichia coli lipopolysaccharide. Tumor necrosis factor-alpha and interleukin-6 levels were quantified at 6 hours and interleukin-10 at 24 hours by enzyme immunoassay. Results were compared with use of the Wilcoxon rank sum test. RESULTS: Tumor necrosis factor-alpha production was significantly higher in whole blood from women with histories of a preterm birth and intra-amniotic infection or inflammation (11,243 +/- 1030 pg/mL [mean +/- SEM]) compared with control subjects (3649 +/- 349 pg/mL) at a lipopolysaccharide concentration of 1 microg/mL (P =.002). There were no significant differences in interleukin-6 or interleukin-10 production. CONCLUSION: Women with previous early preterm deliveries who had evidence of intra-amniotic infection or inflammation had significantly higher tumor necrosis factor-alpha production after lipopolysaccharide stimulation of whole blood compared with women with previous term deliveries.     

肿瘤坏死因子α对脐静脉血管内皮细胞增殖和细胞内游离钙浓度的影响

目的 探讨肿瘤坏死因子α（ＴＮＦ－α）对培养的人脐静脉血管内皮细胞增殖和细胞内游离钙浓度的影响,从细胞间信息传递水平探讨妊娠高血压综合征（妊高征）的发病机理。方法 用终浓度为５００、１０００、２０００Ｕ／ｍｌ的ＴＮＦ－α,将融合成单层的人脐静脉血管内皮细胞进行无血清培养２４ｈ,并以等量的０．０１ｍｏｌ／Ｌ、ｐＨ７．４的磷酸盐缓冲生理盐水作对照,用流式细胞仪测定细胞各周期细胞百分数、荧光分光光度法测定内皮细胞内游离钙浓度。结果 经ＴＮＦ－α作用后的内皮细胞被拉长,由原来的上皮型变为成纤维细胞型,细胞及核边界尚清楚、形态较规则,但在２０００Ｕ／ｍｌ浓度时,可见有细胞脱落及细胞内异常颗粒出现。内皮细胞受到ＴＮＦ－α的刺激后,由Ｇ０＋Ｇ１期进入Ｓ和Ｇ２＋Ｍ期的细胞百分比明显减少,Ｇ０＋Ｇ１期细胞百分数增多,Ｓ和Ｇ２＋Ｍ     

Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys

OBJECTIVE: The purpose of this study was to determine whether treatment with the immune modulators dexamethasone or interleukin-10 prevents interleukin-1beta-induced uterine contractions in a nonhuman primate model. STUDY DESIGN: Thirteen chronically instrumented rhesus monkeys at 135 +/- 1 days of gestation (term, 167 days) received one of three interventions: (1) intra-amniotic interleukin-1beta (10 microg) infusion with maternal dexamethasone (1 mg/kg) intravenously every 6 hours for 1 day before interleukin-1beta and for 2 days thereafter (n = 4), (2) intra-amniotic interleukin-1beta infusion with maternal interleukin-10 (25 microg/kg) given intravenously and 100 microg interleukin-10 given intra-amniotically before the interleukin-1beta and continued every 8 hours for 3 days (n = 5), and (3) intra-amniotic interleukin-1beta administered alone (n = 5). Uterine activity was monitored continuously and quantified as the hourly contraction area (millimeters of mercury times seconds per hour) in all groups until delivery. Amniotic fluid was sampled for leukocyte counts and assayed for prostaglandins E(2) and F(2)alpha, cytokines interleukin-1beta, interleukin-6, interleukin-8, tumor necrosis factor-alpha, interleukin-10, and interleukin-1 receptor antagonist by specific assays. Maternal and fetal blood were assayed for cortisol, dehydroepiandrosterone sulfate, and estradiol. RESULTS: Interleukin-1beta infusion in the absence of immune modulators resulted in an increase in uterine activity and amniotic fluid proinflammatory cytokines, prostaglandins, and leukocytes. Dexamethasone and interleukin-10 treatment significantly reduced interleukin-1beta-induced uterine contractility (P <.05) and amniotic fluid prostaglandins (P <.05) but not interleukin-8 or interleukin-1 receptor antagonist. Amniotic fluid interleukin-6 and maternal and fetal cortisol, dehydroepiandrosterone sulfate, and estradiol concentrations were reduced by dexamethasone (P <.05), whereas tumor necrosis factor-alpha levels and leukocyte counts were attenuated by interleukin-10 treatment (P <.05). An inverse relationship was noted between amniotic fluid interleukin-10 concentrations and interleukin-1beta-induced uterine activity (r = -0.74, P <.05). CONCLUSION: Dexamethasone and interleukin-10 exert similar inhibitory effects on interleukin-1beta-induced uterine activity, which appears to be mediated by a decrease in prostaglandin production. Reduced estrogen biosynthesis or suppression of tumor necrosis factor-alpha and leukocyte migration may contribute to the tocolytic actions of dexamethasone and interleukin-10, respectively. Dexamethasone and interleukin-10 are likely to be useful adjuncts in the treatment of preterm labor that is associated with inflammation or infection.