炎性因子及补体成分在心肌梗死发病机制中的作用探讨

目的探讨IL-8、TNF-α及sC5b-9在心肌梗死发病机制中的作用。方法用双抗体夹心酶联免疫吸附法对38例AMI患者及40名健康人进行IL-8、TNF-α及sC5b-9测定。结果AMI患者血清IL-8、TNF-α及sC5b-9含量明显升高，与健康人比较有显著性差异(P＜0.01)；在AMI发病后第7天，IL-8、TNF-α及sC5b-9水平逐渐下降，到第28天上述变化仍未达到对照组水平。结论IL-8、TNF-α及sC5b-9参与心肌缺血的形成，并与心肌坏死的范围成正相关。抗炎药物治疗有助于AMI患者的恢复。     

急性缺血性脑梗塞患者血液补体活性及TNF、IL-8水平的临床研究

目的：探讨急性缺血性脑梗塞（AIS）患者血液补体成份（sC5b-9)活性及TNF、IL-8水平及其相关性。方法：75例急性脑梗塞患者血浆补体成份测定采用ELISA法测定，血清TNF和IL-8采用放射免疫分析法测定。结果：75例AIS患者血浆sC5b-9和血清TNF、IL-8含量明显升高，与对照组比较有非常显著性的差异（P〈0.01)；两周后仍维持在较高的水平。AIS患者血浆sC5b-9和血清TNF、IL-8含量增高有较好的相关性。结论：结果提示AIS患者血浆sC5b-9和血清TNF、IL-8含量的升高在急性脑梗塞的发病过程中及发病后介导的脑组织损伤过程中起到较为重要的作用。检测AIS患者血浆sC5b-9和血清TNF、IL-8的含量对临床治疗和预后期望值有一定的指导意义。     

原发性免疫性血小板减少症患者外周血microRNAs的表达及与Th1/Th2失衡的关系

目的:探讨原发性免疫性血小板减少症(ITP)患者外周血micoRNAs的表达量与Th1/Th2失衡的关系。方法:纳入30例ITP患者(ITP组)及15例健康人(对照组),采用实时定量PCR(RT-PCR)法检测2组外周血中6种miRNA(miR-107、miR-205-5p、miR-138-5p、miR-326、miR-1827、miR-185-5p)和Th1特异性转录因子T-bet、Th2特异性转录因子GATA-3的表达水平,采用流式细胞术检测Th1、Th2细胞,Aim Plex流式细胞术高通量技术检测Th1细胞因子TNF-α、IFN-γ以及Th2细胞因子IL-4、IL-10含量。比较2组间miRNAs、mRNA、Th1、Th2细胞及其分泌的主要细胞因子的差异,分析ITP患者miRNAs与Th1、Th2细胞及其分泌的主要细胞因子的相关性。结果:与对照组相比,ITP组miRNA(miR-107、miR-205-5p、miR-138-5p、miR-326、miR-1827、miR-185-5p)和Th2细胞特异性转录因子GATA-3的表达水平均显著降低(P0.05); Th1细胞、Th1细胞特异性转录因子T-bet及Th1细胞因子TNF-α表达水平均显著升高(P0.05),T-bet/GATA-3和Th1/Th2比值均显著升高(P0.05)。ITP患者miR-107、miR-205-5p、miR-138-5p相对表达量与Th2细胞均呈负相关(P0.05,r=-0.411; r=-0.593; r=-0.403); miR-1827相对表达量与TNF-α呈负相关(r=-0.390)。结论:ITP患者外周血6种miRNAs表达水平显著降低,导致T-bet mRNA/GATA-3mRNA比值升高,Th1/Th2失衡。     

IL-18及其受体在特发性血小板减少性紫癜患者Th1类细胞优势应答中的作用

目的 探讨白细胞介素18(IL-18)及其受体(IL-18R)在特发性血小板减少性紫癜(ITP)患者Th1类细胞因子优势应答中的作用.方法 应用逆转录聚合酶链反应(RT-PCR)检测15例活动期和18例缓解期ITP患者外周血单个核细胞(PBMNC)中转录因子T-bet和GATA-3 mRNA的表达;应用ELISA法检测血浆中IL-18的变化;应用流式细胞术检测CD3+细胞和淋巴细胞表面IL-18R的表达.13名健康志愿者为正常对照.结果 ITP活动期患者PBMNC中T-bet mRNA表达水平(0.069±0.013)明显高于对照组(0.019±0.010)(P＜0.05),而GATA-3 mRNA的表达水平(0.002±0.001)明显低于对照组(0.005±0.002)(P＜0.05);血浆IL-18和CD3+细胞表面IL-18R表达水平较ITP缓解期患者和对照组显著增高.ITP缓解期患者T-bet与GATA-3 mRNA表达水平与对照组比较差异均无统计学意义(P值均＞0.05),T-bet/GATA-3比例基本恢复正常,血浆中IL-18和CD3+细胞表面IL-18R的表达水平也基本恢复正常.结论 ITP活动期患者表现为Th1优势应答,T-bet/GATA-3比例明显失衡,T-bet/GATA-3比例可作为ITP患者Th1类细胞极化的敏感指标;ITP活动期患者IL-18和IL-18R表达上调,可能为ITP患者的治疗提供一个新的治疗靶点.     

rhTPO对原发性免疫性血小板减少性紫癜患者T、B淋巴细胞免疫功能的影响

目的:探讨ITP患者使用重组人血小板生成素(rhTPO)治疗前、后外周血Th1和Th2细胞因子及B淋巴细胞水平变化及其临床意义。方法:采用CBA技术检测48例ITP患者治疗前后及正常对照组35例外周血Th1和Th2细胞因子水平及B淋巴细胞数的变化,结果:治疗前48例ITP组外周血Th1细胞因子水平明显高于正常对照组,而Th2细胞因子明显低于正常对照组,B淋巴细胞数明显高于正常对照组,差异均具有统计学意义(P0.05);外周血CD19+细胞和CD5+CD19+细胞数及IL-2水平与血小板数呈负相关(r=-0.75),IL-4与血小板数呈正相关(r=0.81),经rhTPO治疗后Th1细胞因子水平及外周血CD19+和CD5+CD19+细胞数均较治疗前明显下降,Th2细胞因子水平较治疗前明显上升(P0.05);结论:ITP患者外周血Th1和Th2细胞因子异常表达及B淋巴细胞数明显升高,ITP病情严重程度与Th1和Th2细胞因子及B淋巴细胞相关。TPO治疗后血小板数上升,可能通过调节ITP患者外周血Th1和Th2免疫平衡及B淋巴细胞水平而发挥作用。     

妊娠合并原发免疫性血小板减少症患者的临床特点分析及T细胞分泌细胞因子水平的研究

目的 :研究妊娠合并原发免疫性血小板减少症(immune thrombocytopenia,ITP)(原发ITP,以下简称为ITP)患者的临床特点及围产期结局,同时研究T细胞分泌细胞因子水平的变化与发病间的关系。方法 :回顾性总结25例妊娠合并ITP患者、8例非妊娠的ITP患者及11例正常孕妇的临床资料,利用蛋白芯片技术检测其T细胞分泌的代表性细胞因子表达水平,并分析妊娠合并ITP患者的T细胞功能变化与其妊娠合并ITP发病间的关系。结果:13例患者(13/25)为妊娠前即有ITP病史,另12例(12/25)则于妊娠期间诊断为ITP;25例患者中的16例(64%)接受了ITP治疗,共分娩了24名新生儿,1例死胎,母亲血小板计数与新生儿间的血小板计数无相关性;蛋白芯片检测结果显示,妊娠合并ITP患者与正常孕妇相比,其肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白细胞介素2(interleukin 2,IL-2)、IL-5、IL-6水平显著升高,IL-12p40和IL-16显著降低;同时,妊娠合并ITP患者与非妊娠期ITP患者相比,其IL-1α、IL-10及IL-13水平显著降低。结论:多数ITP孕妇母婴结局良好。T细胞分泌细胞因子水平的变化可能通过T细胞功能变化参与了妊娠合并ITP患者的发病机制,其中Th1细胞、Th17细胞及CD8+T细胞分泌的相关细胞因子水平升高可能是妊娠合并ITP患者的发病机制之一。     

先兆流产孕妇Th1／Th2细胞因子平衡状况分析

目的探讨辅助T细胞1（Th1）、辅助T细胞2（Th2）型细胞因子平衡与正常妊娠及先兆流产之间的关系。方法采用酶联免疫吸附试验（ELISA）检测60例先兆流产妇女和42名正常妊娠妇女血清中Th1型细胞因子（IL-2、TNF-α及Th2型细胞因子（IL4、IL-10）的表达水平。结果与正常妊娠组相比,先兆流产组血清中IL-2和TNF-α的表达水平明显升高（P均〈0．05）;而2组之间IL-4和IL-10的表达水平差异无统计学意义（P〉0．05）。Th1型细胞因子与Th2型细胞因子平衡向Th1的方向移动。结论Th1／Th2型细胞因子的病理性失衡可能与先兆流产的发生有-定关系。     

Th17细胞在特发性血小板减少性紫癜发病中的作用和意义

目的:本研究探讨Th17细胞在特发性血小板减少性紫癜(ITP)发病中的作用和意义。方法:采用FCM检测ITP患者组和正常对照组外周血中Th17细胞的比例;ELISA技术检测上述两组血浆中IL-17、IL-23、IL-6和TGF-β1的表达水平;RT-PCR技术检测外周血单个核细胞(PBMNC)中IL-17和RORγt mRNA的表达水平;Westernblot法检测PBMNC中pSTAT3和RORγt蛋白的表达水平。结果:ITP患者外周血Th17细胞比例较正常对照组显著升高,血浆中IL-17、IL-23、IL-6和TGF-β1水平明显高于正常对照组(P0.01);ITP患者PBMNC中IL-17和RORγt mRNA表达水平明显高于正常对照组(P0.05);p STAT3和RORγt蛋白的表达水平明显高于正常对照组(P0.05))。结论:在ITP发生和发展中,Thl7细胞亚群比例增高可能是一个重要的决定因素,Th17细胞相关的细胞因子及转录调控因子水平的变化与ITP发病密切相关。     

胶质瘤细胞中Th1/Th2类细胞因子漂移现象的研究

目的：研究Th1、Th2漂移与脑胶质瘤细胞的发生发展及治疗诊断中作用。方法：采用RT-PCR技术对10株脑胶质瘤细胞进行了IL-4、IL-6、IL-10和TNF-α检测。结果：在脑胶质瘤细胞株中Th2类细胞因子mRNA强势表达，IL-4、IL-5、IL-10和TNF-α的表达率分别为90％(9／10)，70％(70／10)，90％(9／10)，0％(0／10)。结论：肿瘤细胞发生明显的Th2／Tn1漂移现象，造成机体的免疫抑制，有利于肿瘤细胞的免疫逃逸。     

老年带状疱疹后神经痛病人外周血Th17/Treg细胞及相关细胞因子的表达

目的:探讨老年带状疱疹后神经痛(postherpetic neuralgia, PHN)病人外周血中Th17、Treg细胞及相关细胞因子的表达及其临床意义。方法:采用流式细胞术检测60例老年带状疱疹后神经痛病人及30例健康对照者外周血中Th17、Treg细胞水平,并计算Th17/Treg比率,ELISA方法检测外周血中白介素-6 (Interleukin-6, IL-6)、白介素-10 (Interleukin-10, IL-10)、白介素-17 (Interleukin-17,IL-17)及人肿瘤坏死因子-α(TNF-α)的表达水平。结果:与对照组相比,病例组病人外周血Th17的含量及IL-6、IL-17表达水平显著降低(P <0.05);Treg细胞含量及IL-10、TNF-α表达水平显著升高(P <0.05),且Th17/Treg比率较对照组降低,差异具有统计学意义(P <0.05)。结论:Th17细胞在PHN外周血中显著降低,Treg细胞显著增高,与二者相关的细胞因子也相应变化,Th17/Treg比率显著降低,提示两者通过多种机制参与机体的免疫应答,Th17/Treg的失衡可能在老年PHN的发病机制中起重要作用。     

免疫性血小板减少症患者白介素-22及相关CD4~+ T细胞亚群的表达

本研究通过检测初治的成人免疫性血小板减少症(ITP)患者外周血中白介素-22(IL-22)及相关CD4+T细胞亚群的表达,探讨其在ITP发病机制中的作用。以我院住院治疗的40例新诊断的急性ITP患者及40例健康对照者为研究对象,应用ELISA法检测外周血血浆中IL-22的含量,采用流式细胞术检测Th1、Th17、Th22细胞亚群的比例,并分析其相关性。结果表明,新诊断的ITP患者血浆中IL-22的含量为(364.12±94.22)pg/ml,显著高于健康对照者(P<0.001);ITP患者外周血Th1细胞比例为(18.92±6.03)%,Th22细胞比例为(2.28±0.51)%,显著高于健康对照者(P<0.05);且ITP患者血浆IL-22水平与Th1和Th22细胞比例之间存在正相关(Th1:r=0.42,P=0.022;Th22:r=0.40,P=0.030);而ITP患者Th17细胞比例与健康对照者比较无明显差异,且与IL-22水平无相关性。结论:成人ITP患者外周血中IL-22水平明显升高,且与Th1、Th22细胞比例之间密切相关,提示IL-22与Th1和Th22细胞在ITP的发病中可能起着协同作用,而Th17细胞可能与ITP的发病无关。     

Cytokines in the pathogenesis of malaria: levels of IL-I beta, IL-4, IL-6, TNF-alpha and IFN-gamma in plasma of healthy individuals and malaria patients in a holoendemic area.

A longitudinal study was conducted between October 1989 and February 1990 in a malaria holoendemic area of Gabon to determine the plasma concentration of various cytokines in individuals continuously exposed to infection with malaria parasites. No cases of severe malaria were seen and fever was the main presenting symptom of clinical malaria. Parasite rates were highest in children 6-9 years old but clinical malaria was seen essentially in children below 6 years of age. The incidence of clinical malaria was highest in November and February corresponding to the beginning and end of heavy rains respectively. Parasite rates did not show any seasonal variations. Overall, there was no seasonal variation in plasma cytokine levels but both IL-6 and IL-4 levels were highest in February. Plasma concentration of TNF-alpha and IFN-gamma were higher in parasitaemic than aparasitaemic individuals and donors who had clinical malaria had higher levels of TNF-alpha, IFN-gamma and IL-6 than asymptomatic parasitaemic donors. There was a negative correlation between age of the individual and the concentration of plasma TNF-alpha and IFN-gamma suggesting that the production of these cytokines could be modulated by repeated malarial infections. Asymptomatic parasitaemic children 5-7 years of age had higher levels of plasma TNF-alpha than clinically similar children below or above this age group suggesting that refractoriness to the clinical effects of TNF-alpha may be an important factor in the ability of these children to resist clinical malaria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of platelet immunity in patients with SLE and with ITP

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15-20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-alpha in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of differences in the immunopathogenesis between SLE-TP and ITP.     

糖皮质激素对ITP初治患者T辅助细胞相关细胞因子基因表达的影响

本研究旨在探讨免疫性血小板减少性紫癜(ITP)患者中T辅助细胞(helper T cell,Th)细胞免疫状态以及其与治疗反应的关系。应用实时荧光定量RT-PCR方法检测20例初发ITP患者(男性8例,女性12例,中位年龄41.0岁)接受糖皮质激素治疗[泼尼松1mg/(kg.d)]前后以及20例正常对照者外周血单个核细胞中Th细胞相关基因(T-bet、IFN-γ、GATA-3、TGF-β、Foxp3、IL-2、IL-4)表达水平的变化。结果表明:治疗前ITP患者外周血单个核细胞中T-bet、IFN-γ、IL-2表达较正常对照明显升高,差异有显著统计学意义(p<0.01),治疗后患者T-bet、IFN-γ、IL-2表达较治疗前降低(p<0.05);治疗前Foxp3表达较正常无明显变化,治疗后Foxp3表达较治疗前升高(p<0.05)。治疗前患者TGF-β的表达与正常对照相比无明显差别,治疗后老年患者与年轻患者中呈现不同的变化模式,年龄<60岁患者治疗后TGF-β表达水平较治疗前降低(p<0.05),而年龄≥60岁患者TGF-β较治疗前升高。结论:ITP患者存在Th细胞亚群失衡,常规糖皮质激素治疗仍是针对初治IT...     

特发性血小板减少性紫癜患者外周血淋巴细胞共刺激分子的表达及白介素18的作用

本研究探讨特发性血小板减少性紫癜（ITP）患者外周血淋巴细胞共刺激分子CD80、CD86及其配体CD28的表达水平及白介素18的作用。应用免疫荧光标记和流式细胞技术检测34例ITP患者和34名正常人外周血淋巴细胞共刺激分子CD80、CD86及其配体CD28的表达,酶联免疫（ELISA）法测定血浆IL-18。结果表明：ITP患者外周血淋巴细胞CD80、CD86表达率（4.21±2.27%,7.19±5.16%）均明显高于正常对照组（2.34±0.87%,4.08±1.96%,P〈0.01）。ITP组血浆IL-18含量为（538.31±111.33）pg/ml,正常对照组血浆IL-18含量为（489.44±49.07）pg/ml。IL-18含量与血小板数量呈显著性负相关（r=-0.395,P〈0.05）。结论：ITP患者CD80和CD86共刺激分子过度表达,患者血浆中IL-18水平比正常对照组明显升高（P〈0.05）,共刺激分子CD80、CD86与ITP发病密切相关,IL-18在ITP发病机理中起重要作用。     

重型再生障碍性贫血患者骨髓中辅助性T细胞亚群数量及功能的变化

目的　研究重型再生障碍性贫血 (SAA)患者在免疫抑制治疗 (IST)恢复前后骨髓中辅助性T细胞 (Th细胞 )亚群改变情况及与造血功能的关系。方法　以流式细胞仪测定 2 4例发病期、15例恢复期SAA患者及 16名正常对照者骨髓中Th细胞亚群及CD3 CD8 细胞改变情况 ;以放射免疫法测定 2 0例发病期SAA患者、12例IST后恢复期患者及 16名正常对照者血清中TNF α、IL 4水平 ;评价Th1与CD3 CD8 细胞、TNF α的相关关系 ;评价Th1、CD3 CD8 细胞、TNF α、IL 4及Th1/Th2平衡与网织红细胞、中性粒细胞绝对值的相关关系。结果　正常对照组骨髓中Th1细胞、Th2细胞百分率及Th1/Th2比值分别为 (0 .4 2± 0 .30 ) %、(0 .2 4± 0 .17) %、1.5 7± 0 .93;发病期SAA分别为 (4 .87± 2 .6 4 ) %、(0 .4 1±0 .2 6 ) %、2 1.2 2± 5 .0 7,均显著多于正常对照 (P <0 .0 1,P <0 .0 5 ,P <0 .0 1) ,恢复期分别为 (0 .5 3± 0 .2 2 ) %、(0 .4 4± 0 .15 ) %、1.38± 0 .4 5 ,与正常对照组相当 (P均 >0 .0 5 ) ;CD3 CD8 细胞亦由发病期的(32 .32± 18.6 9) %显著下降为 (13.76± 2 .96 ) % (P <0 .0 1) ;SAA发病期血清中TNF α、IL 4为 (4 .2 9± 3.15 ) μg/L、(1.2 4± 0 .73) μg/L ,高于正常对照组的 (1.2 1± 1.16 ) μg/L     

ITP患者脾细胞分泌IL-18及IL-18结合蛋白的研究

本研究旨在探讨特发性血小板减少性紫癜(ITP)脾脏单个核细胞培养后IL-18,IL-18结合蛋白(b ind ingprotein,BP),IFN-γ,IL-4等细胞因子的表达及其临床意义。常规无菌制备脾单个核细胞,置含PHA(phytohem agg lutinin)10μg/m l,10%胎牛血清的RPM I1640完全培养基中,于37℃、5%CO2条件下培养;分析ITP患者及正常对照者脾单个核细胞分泌细胞因子的差异。结果表明:脾单个核细胞培养48小时后,ITP患者IL-18和IFN-γ的含量较正常对照者明显升高;IL-18BP含量两组间差异无统计学意义(p=0.646);IL-4低于检测限。结论:IL-18、IL-18BP等细胞因子表达失衡在ITP的免疫紊乱和发生发展中起着一定的作用。     

Cytokine regulation of immune response in patients with acute HCV-infection

AIM: To study the cytokine spectrum (IL-1beta, IL-2, IL-4, IL-6, TNF-alpha, interferon-alpha, interferon gamma) in patients with acute hepatitis C (AHC). MATERIAL AND METHODS: Peripheral blood from 70 AHC patients was studied for cytokines using enzyme immunoassay (kits made by Protein contur, St-Petersburg). RESULTS. A primary examination in all the patients who finally recovered detected high levels of IL-2, IL-6, interferon-gamma, normal levels of IL-4. This evidenced for marked activity of Th1-lymphocytes, depressed synthesis of Th2-mediators stimulating immune response and elimination of the virus. AHC patients who later developed chronic disease had less frequent rise of proinflammatory mediators, but more frequent high IL-4 levels. Such features of immune response reflected higher activity of Th2-lymphocytes inhibiting Th1-effector mechanisms. This promoted active virus replication and formation of chronic hepatitis C. CONCLUSION: Determination of cytokine spectrum in AHC has a prognostic implication.