Th1/Th2在结核性脑膜炎发病过程中的变化及临床意义

目的分析结核性脑膜炎患者CD4+T淋巴细胞的亚型(Th1/Th2)细胞及其Th1型细胞因子IFN-γ和Th2型细胞因子IL-4在血及脑脊液中的分布特点,探讨系统及局部的Th1/Th2免疫应答在人类结核性脑膜炎病理生理过程中的可能作用。方法利用流式细胞术测定结核性脑膜炎组治疗前、治疗3个月后外周血及脑脊液标本中Th1/Th2的百分含量,同时,应用流式微珠阵列(cyto-metric bead array,CBA)测定血清及脑脊液标本中IFN-γI、L-4的浓度,并测定30例健康对照组外周血中Th1/Th2细胞的百分含量与IFN-γI、L-4的浓度进行对照。结果(1)结核性脑膜炎组治疗前外周血Th1、Th2细胞水平、血清IFN-γ、IL-4的浓度(中位数)治疗前分别为3.8%±0.9%、2.03%±1.51%、29.05、55.05 ng/L;治疗3个月后分别为4.0%±0.8%、1.6%±1.1%、30.60、52.70 ng/L;健康对照组为6.3%±2.6%、1.7%±0.6%、65.95 ng/L、50.30 ng/L。同健康对照组比较,结核性脑膜炎组外周血中Th1水平、血清IFN-γ浓度显著降低(P<0...     

Th细胞免疫与结核性胸膜炎胸膜粘连关系的研究

目的 探讨胸腔积液辅助性T细胞(Th细胞)免疫与结核性胸膜炎胸膜粘连的关系.方法 用双抗体夹心酶联免疫吸附试验(ELISA)法测定汕头大学医学院第一附属医院、潮南民生医院2005年9月至2006年11月住院的结核性胸膜炎患者44例(结核组)和恶性胸腔积液患者22例(恶性组)胸腔积液干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)质量浓度.依据影像学检查是否存在包裹性胸腔积液,将结核组进一步分为包裹组(23例)和游离组(21例).结果 结核组IFN-γ质量浓度显著高于恶性组[(1238.7±807.2)ng/L对(87.8±64.8)ng/L,P＜0.01],而IL-4质量浓度在两组间差异无显著性意义.结核性胸膜炎病程＜1个月的包裹组胸腔积液IFN-γ质量浓度显著高于相应游离组[(1961.9±1008.1)ng/L对(1140.8±327.4)ng/L,P＜0.01],病程1个月后这种差异不明显,而IL-4质量浓度在结核性胸膜炎各亚组间均未发现显著差异.病程≥1个月患者胸膜粘连发生率高于病程＜1个月者(58.82%对48.15%),但差异无显著性意义(P＞0.05).结论 结核性胸膜炎局部Th1免疫增强,在病程早期尤其明显,但过强的Th1免疫易导致胸膜粘连;Th2免疫在结核性胸膜炎局部无明显变化.     

Th1/Th2在结核性脑膜炎发病过程中的变化及临床意义

目的 分析结核性脑膜炎患者CD4⁺T淋巴细胞的亚型(Th1/Th2)细胞及其Th1型细胞因子IFN-γ和Th2型细胞因子IL-4在血及脑脊液中的分布特点,探讨系统及局部的Th1/Th2免疫应答在人类结核性脑膜炎病理生理过程中的可能作用。方法 利用流式细胞术测定结核性脑膜炎组治疗前、治疗3个月后外周血及脑脊液标本中Th1/Th2的百分含量,同时,应用流式微珠阵列(cyto-metric bead array,CBA)测定血清及脑脊液标本中IFN-γI、L-4的浓度,并测定30例健康对照组外周血中Th1/Th2细胞的百分含量与IFN-γI、L-4的浓度进行对照。结果 (1)结核性脑膜炎组治疗前外周血Th1、Th2细胞水平、血清IFN-γ、IL-4的浓度(中位数)治疗前分别为3.8%±0.9%、2.03%±1.51%、29.05、55.05 ng/L;治疗3个月后分别为4.0%±0.8%、1.6%±1.1%、30.60、52.70 ng/L;健康对照组为6.3%±2.6%、1.7%±0.6%、65.95 ng/L、50.30 ng/L。同健康对照组比较,结核性脑膜炎组外周血中Th1水平、血清IFN-γ浓度显著降低(P<0.05),结核性脑膜炎组治疗前与治疗3个月后外周血中Th1、Th2水平、血清IFN-γI、L-4浓度差异均无统计学意义(P>0.05)。(2)25例结核性脑膜炎组治疗前、后脑脊液标本中Th1细胞水平分别为8.4%±4.6%、7.1%±4.4%,治疗3个月后脑脊液中Th1细胞水平显著降低(P<0.05)。(3)30例结核性脑膜炎组治疗前、后脑脊液标本中IFN-γ的浓度分别为176.45 ng/L、75.50 ng/L,治疗后明显降低(P<0.05)。结论 结核性脑膜炎组外周血Th1应答比健康对照组低;结核性脑膜炎组治疗后Th1应答比治疗前减弱,他们之间的因果关系尚待进一步研究。     

无免疫功能低下的肺隐球菌病患者Th1/Th2类细胞因子的变化

目的 分析无免疫功能低下的肺隐球菌病(PC)患者Th1/Th2类细胞因子的变化及其机制.方法 应用酶联免疫吸附测定(ELISA)法测定20例无免疫功能低下的PC患者(PC组)血清中IL-12、γ-干扰素(IFN-γ)和IL-4的浓度,并与20名健康体检者(对照组)进行对比.分离PC组和对照组外周血单个核细胞(PBMC),重组人IL-12 (rhIL-12)刺激48 h后收集上清液,应用ELISA法测定各组培养上清液中IFN-γ和IL-4的浓度.结果 (1)无免疫功能低下的PC患者血清IFN-γ的浓度为(14.5±2.7) ng/L,显著低于对照组的(81.8±9.8) ng/L,差异有统计学意义(t=6.590,P＜0.01),PC组和对照组血清IL-12浓度分别为(2.5±0.5)和(2.5±0.6) ng/L,血清IL-4浓度分别为(6.9±1.3)和(7.3±1.5) ng/L,差异均无统计学意义(t值分别为0.0035和0.2136,均P＞0.05).(2)PC组与对照组PBMC上清液中IFN-γ浓度分别为(55.7 ±13.6)和(51.1±17.5) ng/L,IL-4分别为(5.1±0.7)和(5.0±0.6)ng/L,差异均无统计学意义(t值分别为0.2979和0.0325,均P＞0.05).(3)经rhIL-12刺激后,PC组和对照组PBMC上清液中IFN-γ的浓度均有明显增高,为(4.3±0.5)和(7.9±1.1)倍,PC组增高幅度明显低于对照组,差异有统计学意义(t=3.01,P＜0.01);而IL-4的浓度两组分别增加了(0.9±0.4)和(1.3±0.4)倍,差异无统计学意义(t=0.7240,P＞0.05).结论 无免疫功能低下的PC患者血清Th1类因子(IFN-γ)下降,Th2类因子(IL-4)无明显变化;Th1细胞对IL-12的反应性和敏感性下降可能是血清Th1类因子(IFN-γ)下降的原因之一.     

拉米夫定治疗对慢性乙型肝炎患者干扰素-γ和白细胞介素-4的影响

目的 观察拉米夫定治疗慢性乙型肝炎患者血清IFN-γ和IL-4水平的动态变化.方法 ELISA法分别检测66例慢性乙型肝炎患者在拉米夫定治疗前,治疗后第3、6、9、12个月时的血清IFN-γ和IL-4水平.选取20名健康献血员作为健康对照.治疗前后比较用t检验,计数资料采用非参数秩和检验.结果 HBeAg阳性患者拉米夫定治疗前.完全应答组IFN-γ水平为(21.03±4.44)ng/L,明显高于部分应答组的(13.85±3.92)ng/L及无应答组的(10.63±3.11)ng/L(t=7.56,t=11.87,均P<0.01);以IFN-γ为15.66 ng/L为界,治疗前IFN-γ高水平患者完全应答率明显高于低水平患者(31.0%比8.7%,x2=8.391,P<0.01),无应答率明显低于低水平患者(13.8%比52.2%,x2=4.256,P<0.01).治疗后完全应答组患者IFN-γ/IL-4接近或高于对照组,部分应答组和无应答组低于对照组;HBeAg阴性患者拉米夫定治疗后IFN-γ/IL-4缓慢上升,但未达对照组水平.结论 拉米夫定治疗慢性乙型肝炎可增加IFN-γ释放,抑制IL-4释放,治疗应答程度与治疗后辅助性T淋巴细胞(Th)1/Th2平衡的恢复及治疗前IFN-γ水平有关.     

拉米夫定对慢性乙型肝炎的抗病毒疗效与Th1/Th2变化的关系

目的观察拉米夫定（LAM）治疗前后患者血清Th1/Th2比值的动态变化。方法用酶联免疫吸附（ELISA）方法分别检测60例慢性乙型肝炎患者在拉米夫定治疗前,治疗后第3、6、9、12月时的血清IFN-γ和IL-4水平。选取20名健康献血员作为正常对照。结果LAM治疗前ALT高水平组IFN-γ水平及IFN-γ/IL-4比值较高,完全应答率较高,无应答率较低;治疗后完全应答组IFN-γ/IL-4水平接近或高于对照组,部分应答组和无应答组IFN-γ/IL-4水平低于对照组。结论拉米夫定治疗慢性乙型肝炎可增加Th1类细胞因子IFN-γ分泌,抑制Th2类细胞因子IL-4分泌,治疗后Th1/Th2平衡的恢复与抗病毒疗效有关。T细胞免疫功能的恢复是抗病毒治疗的关键之一。     

儿童支气管哮喘血清IL-4、IL-10和IFN-γ浓度的测定及其临床意义

目的探讨血清白介素4（IL-4）、IL-10和干扰素γ（IFN-γ）与支气管哮喘（简称哮喘）的关系及其临床意义。方法随机收集于2008年6月至2009年1月期间在山东大学齐鲁儿童医院就诊的哮喘患儿纳入哮喘组,哮喘诊断全部符合2003年中华医学会儿科分会呼吸学组修订的支气管哮喘诊断标准,共计47例。同时选取性别和年龄与哮喘组匹配的51例健康体检儿童作为正常对照组。收集外周静脉血,采用双抗体夹心ELISA方法测定两组血清IL-4、IL-10、IFN-γ浓度,比较两组之间血清IL-4、IL-10、IFN-γ浓度的差异。结果哮喘组血清IL-4浓度[（346.74±82.92）ng/L]显著高于正常对照组[（199.87±59.25）ng/L]（P〈0.01）;哮喘组血清IL-10浓度[（86.38±58.58）ng/L]与正常对照组[（98.77±37.05）ng/L]的差异无统计学意义（P〉0.05）,哮喘组血清IFN-γ浓度[（94.51±22.92）ng/L]低于正常对照组[（110.75±47.11）ng/L]（P〈0.05）。结论 Th2类细胞因子IL-4在哮喘患儿血清中浓度升高,而Th1类细胞因子IFN-γ浓度下降,哮喘患儿存在Th1/Th2细胞免疫失衡;血清IL-4、IFN-γ浓度检测可以作为儿童哮喘的辅助诊断手段,同时本研究为使用抗IL-4制剂、补充IFN-γ等免疫学方法治疗哮喘提供依据。     

流式微珠阵列法检测结脑患者Th1/Th2细胞因子表达

目的:运用流式微珠阵列法评价IFN-γ、IL-4在结核性脑膜炎(结脑)中的表达情况,以探讨Th1/Th2平衡状态与其疾病发生发展的关系。方法:采集结脑患者治疗前后的外周血和脑脊液以及健康人的外周血,流式微珠阵列法检测其中IL-4和IFN-γ的浓度,比较各检测指标在各组中差异,并分析差异的意义。结果:结脑患者外周血的IFN-γ浓度较正常对照组低,IL-4浓度无差异;治疗前后外周血中的IFN-γ、IL-4和脑脊液中的IL-4水平均差异无统计学意义,但治疗前后脑脊液中IFN-γ表达差异有统计学意义。结论:与正常对照组及治疗前后相比较,Th1细胞因子IFN-γ在结脑患者的体液中有显著性变化,提示其参与结脑的病理生理过程;流式微珠阵列法能准确检测Th1/Th2细胞因子表达的动态变化。     

KL-6和Th1/Th2细胞因子在结缔组织病相关性间质性肺炎中的表达及临床意义

目的探讨涎液化糖链抗原(KL-6)与1型辅助性T细胞/2型辅助性T细胞(Th1/Th2)细胞因子在结缔组织病相关性间质性肺炎(CTD-IP)中的表达及临床意义。 方法选择2017.01至2019.01间收治的77例CTD-IP患者纳为CTD-IP组,60例无肺间质病变CTD者纳为CTD组,50例健康体检合格者为健康组,比较三组血清涎液化糖链抗原(KL-6)、Th1细胞因子γ干扰素(IFN-γ)、Th2细胞因子白介素-4(IL-4)及Th1/Th2(IFN-γ/IL-4)水平,并根据CTD-IP患者肺通气障碍、肺弥散功能障碍严重程度及影像学表现,对CTD-IP组患者进行分组,统计CTD-IP患者血清KL-6、IFN-γ、IL-4及IFN-γ/IL-4表达水平,并分析以上血清物质在评估CTD-IP患者病情中的效果。 结果健康对照组、CTD组及CTD-IP组中,血清KL-6及IL-4水平呈依次上升趋势,IFN-γ及IFN-γ/IL-4水平呈依次下降趋势,组间差异均显著(P<0.05);CTD-IP患者肺通气轻度障碍组、中度障碍组及重度障碍组中,血清KL-6及IL-4水平呈依次上升趋势,IFN-γ及IFN-γ/IL-4水平呈依次下降趋势,组间差异均显著(P<0.05);CTD-IP患者肺弥散轻度障碍组、中度障碍组及重度障碍组中,血清KL-6及IL-4水平呈依次上升趋势,IFN-γ及IFN-γ/IL-4水平呈依次下降趋势,组间差异均显著(P<0.05);CTD-IP患者HRCT表现活动性组血清KL-6、IFN-γ、IFN-γ/IL-4水平明显高于非活动性组(P<0.05),IL-4水平显著低于非活动性组(P<0.05)。 结论血清KL-6、IFN-γ、IL-6及IFN-γ/IL-6水平在反映CTD-IP患者肺通气功能障碍、肺弥散功能障碍、疾病活动期中具有良好应用价值,可作为反映CTD-IP患者病情的可靠血清参考物质。     

紫外线照射充氧自血回输对脑梗死患者Th1/Th2细胞因子的影响

目的　探讨紫外线照射充氧自血回输(UBIO)治疗对脑梗死患者Th1/ Th2细胞因子的影响。方法　采用EL ISA法检测脑梗死患者外周血单个核细胞(PBMC)培养上清液及血清中IFN-γ、IL - 4水平。结果　在PBMC培养上清液中,UBIO组治疗后IFN- γ水平为(177.2±11.9) ng/ L,与UBIO组治疗前的(191.1±19.9) ng/L、对照组(190 .8±2 5 .3) ng/ L和正常组的(198.5±16 .7) ng/ L相比较有显著性差异(P<0 .0 5 )。IL - 4水平UBIo组治疗前为(5 7.1±19.6 ) ng/ L、治疗后(5 4 .9±18.8) ng/ L 及对照组(5 9.4±2 1.4 ) ng/ L 均低于正常组(82 .8±30 .7) ng/ L (P<0 .0 5 )。血清中IL - 4水平UBIO组治疗后为(4.86±2 .31) ng/ L ,高于正常组(3.32±2 .0 9) ng/ L (P<0 .0 5 )。其余各组间无显著性差异(P>0 .0 5 )。结论　脑梗死患者Th1 / Th2 平衡倾向于Th1 ,UBIo治疗可下调Th1 细胞活性,使Th1 / Th2 趋于平衡。     

白细胞介素7和15对肺结核患者Th1/Th2平衡的调节作用

目的探讨白细胞介素7(IL7)、IL15对肺结核病患者外周血单个核细胞(PBMC)分泌Th1型细胞因子γ干扰素(IFNγ)、肿瘤坏死因子α(TNFα)和Th2型细胞因子IL4、IL10的影响。方法选择2003年1至9月入院的60例肺结核患者和25名健康对照者,用葡聚糖泛影葡胺密度梯度离心法分离PBMC。按加入刺激物的不同,将每份标本分为6组:RPMI1640组、纯化蛋白衍生物(PPD组)、PPD+IL7组、PPD+IL7抗体组、PPD+IL15组、PPD+IL15抗体组。加入相应刺激物后培养72h,收集上清液,采用酶联免疫吸附法(ELISA)检测各组培养上清液中IFNγ、TNFα、IL4、IL10的水平。结果与PPD组相比,加入IL7的患者组PBMC分泌IFNγ和TNFα显著增高,分别为(107±42)～(157±74)ng/L、(460±128)～(887±242)ng/L;显著抑制IL4和IL10的合成,分别为(58±15)～(31±9)ng/L、(153±40)～(112±32)ng/L。健康对照组PBMC分泌IFNγ和TNFα显著增高,分别为(211±57)～(292±92)ng/L、(1203±390)～(1722±503)ng/L;显著抑制IL4和IL10的合成,分别为(43±13)～(36±11)ng/L、(135±37)～(96±36)ng/L。加入IL15患者组PBMC分泌IFNγ和TNFα显著增高,分别为(107±42)～(231±62)ng/L、(460±128)～(843±208)ng/L;显著抑制IL4和IL10的合成,分别为(58±15)～(37±9)ng/L、(153±40)～(116±41)ng/L。健康对照组PBMC分泌IFNγ和TNFα显著增高,分别为(211±57)～(343±108)ng/L、(1203±390)～(1468±235)ng/L;显著抑制IL4和IL10的合成,分别为(43±13)～(36±8)ng/L、(135±37)～(90±35)ng/L。加入IL7抗体或IL15抗体均可抑制IFNγ和TNFα的分泌,促进IL4和IL10的合成。肺结核患者各组IFNγ、TNFα水平均低于健康对照各组,而IL4、IL10水平比较差异无统计学意义。结论IL7和IL15可作为免疫调节剂,诱导IFNγ及TNFα分泌,抑制IL4及IL10合成,从而调节Th1/Th2平衡,发挥对结核分枝杆菌感染患者的免疫保护作用。     

肺结核患者的Th1/Th2细胞因子失衡

目的　探讨肺结核患者是否存在Th1/Th2反应失衡 ,以及与病情严重程度和治疗反应的关系。方法　对 10 0名健康对照和 12 4例未经治疗的菌阳肺结核患者检测血清IgE、IL 4和IFN γ ,比较两组间差异并分析其与病情严重程度、治疗后痰菌阴转情况及初复治的关系。结果　肺结核组血清IgE(1.0 4 8± 0 .4 96 )、IL 4 (0 .4 39± 0 .16 0 )显著高于健康对照组 (分别为 0 .86 7± 0 .2 89和 0 .4 2 1±0 0 2 4 ) ,而血清IFN γ(0 .2 13± 0 .0 17)显著低于健康对照组 (0 .2 2 4± 0 .0 0 5 )。病灶范围大或有空洞形成的患者血清IL 4显著高于病灶范围小的患者 ,复治患者IL 4和IFN γ显著低于初治患者。抗结核治疗 2个月后痰菌未转阴组与痰菌阴转组相比 ,前者治疗前血清IL 4较高而IFN γ较低。结论　未经治疗的肺结核患者存在Th1反应减弱 ,Th2反应增强 ,其中病灶范围大或有空洞形成的患者更为显著。而且Th1反应较弱者治疗效果较差。     

Gamma-Interferon and Soluble Interleukin 2 Receptor in Tuberculous Pleural Effusion

To analysis the difference between systemic and local pleural T cell response in pulmonary tuberculosis, we analyzed interferon (IFN)-gamma and soluble interleukin-2 receptor (sIL-2R) in peripheral blood mononuclear cells (PBMC) culture supernatants and in pleural effusion (PE). We also investigated the association of pleural INF-gamma and sIL-2R levels with development of residual pleural thickening (RPT). The subjects in this study included patients with active pulmonary tuberculosis with or without PE (n = 46), those with nontuberculous PE (n = 32), and healthy tuberculin reactors (n = 20). Measurement of IFN-gamma and sIL-2R were made by ELISA. In pulmonary tuberculosis, IFN-gamma and sIL-2R concentrations in PBMC culture supernatants were lower than those of healthy tuberculin reactors (IFN-gamma; 258.4 +/-111.5 pg/mL versus 2792.5 +/-633.2 pg/mL, sIL-2R; 1465.0 +/-144.4 pg/mL versus 4777.1 +/-178.5 pg/mL, p < 0.05), whereas IFN-gamma and sIL-2R concentrations in PE were higher than those from nontuberculous pleural effusion (IFN-gamma; 1154.4 +/-252.4 pg/mL versus 292.0 +/-68.9 pg/mL, sIL-2R; 9805.2 +/-978.9 pg/mL versus 3426.7 +/-695.6 g/mL, p < 0.05). IFN-gamma and sIL-2R in PBMC culture supernatants were significantly lower in tuberculat patients with PE than those without PE, and the patients with a high value of IFN-gamma or sIL-2R in PE showed a low value of IFN-gamma or sIL-2R in PBMC culture supernatant, respectively. Patients with RPT had significantly higher IFN-gamma and sIL-2R values in their PE compared with those without RPT. These findings suggest that diminished systemic Th1 response in tuberculosis results from the accumulation of activated Th1 cell to the disease site, and that levels of IFN-gamma and sIL-2R in PE are useful posttreatment markers of RPT.     

Methimazole upregulates T-cell-derived cytokines without improving the existing Th1/Th2 imbalance in Graves' disease

There is probably a systemic shift of cytokine production in patients with Graves' disease (GD) toward the Th2 cytokine response. Methimazole (MMI) is the first choice for patients with GD and presumably has some direct immunomodulatory action. The aim of this study was to evaluate the balance shift in Th1/Th2 cytokines in patients with GD after 1 yr of MMI treatment, when compared to the same balance in patients with newly diagnosed GD before treatment and in healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated from 17 healthy volunteers, from 18 patients with newly diagnosed GD before treatment and from 15 euthyroid patients with GD after 1 yr of MMI treatment. The PBMC were activated with ionomycin and phorbol 12-myristate 13-acetate (PMA). The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. In conclusion, our results show no significant change in the ratio between Th1 and Th2 cytokines produced by PBMC from patients with GD after 1 yr of MMI treatment, when compared to the ratio before treatment. The ongoing prevalence of the Th2 immune response after treatment speaks against the immunomodulatory action of the drug on the systemic level.     

Th1/Th2 Imbalance and Elevated PD-L1 in Pleural Effusion Predict the Risk of Multi-Drug Resistant Tuberculous Pleuritis

Background: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB). Objective: To determine the significance of Th2/Th1 ratio and concentration of PD-L1 in the pleural effusions for prediction of MDR-TB. Methods: We measured the ratio of Th2 to Th1 T cells from pleural effusions in 373 tuberculous pleuritis patients. We also measured the concentration of programmed death ligand-1 (PD-L1) in the pleural effusions of these patients. Afterwards, we determined the optimal cut-off value for predicting the occurrence of multi-drug resistant tuberculous based on the Youden index, diagnostic evaluation test, and receiver operation curve. Multiple logistic analysis was employed to identify the independent risk factors for MDR-TB occurrence. Results: The area under the curve (AUC) of the Th2 to Th1 ratio was 0.66 and the concentration of PD-L1 was 0.71. Based on the combined detection of PD-L1 concentration in pleural effusion and the Th2 to Th1 ratio, our AUC was 0.81 and had a specificity of 0.92. Only a combined detection was able to identify patients developing multidrug-resistant tuberculosis. Multiple logistic analysis showed that a high concentration of PD-L1 and a high Th2 to Th1 T ratio in pleural effusions were indicative of an immunocompromised status. Therefore, these measurements might be independent risk factors for the occurrence of multidrug-resistant tuberculous. Conclusion: Evaluation of immune status based on PD-L1 pleural concentration and Th2 to Th1 ratio might predict the risk of MDR-TB occurrence.     

白细胞介素12对结核病患者TH1/TH2平衡的影响

目的探讨白细胞介素12(IL-12)对结核病患者外周血单个核细胞(PBMC)分泌干扰素γ(IFN-γ)、白细胞介素4(IL-4)的影响.方法随机将25例结核患者和15名健康人PBMC分为RPMI1 640组、PPD组、PPD+rhIL-12组、PPD+anti-IL-12组,采用ELISA法检测各组培养上清液中IFN-γ、IL-4的水平.结果与PPD组相比,加入rhIL-12能有效增加结核患者及健康人PBMC分泌IFN-γ(分别为321.6±87.7至452.5±111.4, 387.0±70.8至515.4±44.1), 减少IL-4的分泌(54.6±11.0至41.3±13.5,55.1±9.5至38.2±12.7);而加入anti-IL-12可抑制IFN-γ的分泌,促进IL-4合成,且结核患者各组IFN-γ水平均低于健康人各对应组,而IL-4水平无差异.复治组IFN-γ、IL-4水平均低于初治组(P<0.05).结论 IL-12通过诱导IFN-γ分泌,抑制IL-4合成,从而调节TH1/TH2平衡,对结核分支杆菌感染患者产生保护性的免疫反应.IL-12可作为结核免疫调节剂,并可用于开发结核新疫苗.     

白细胞介素12调节小鼠Th1/Th2的抗结核分支杆菌感染研究

目的 观察、评价白细胞介素１２（ＩＬ－１２）对结核分支杆菌感染小鼠细胞因子的影响和疗效。方法 将ＢＡＬＢ／ｃ小鼠４２只,制成小鼠结核分支杆菌感染模型,随机分为对照组（ＰＢＳ）和ＩＬ－１２共两组（２１只）。给予ＰＢＳ或ＩＬ－１２治疗,检测血清γ干扰素（ＩＮＦ－γ）、ＩＬ－４、ＩＬ－１０水平（ＥＬＩＳＡ法）和器官菌数计数,观察治疗后生存率。结果 ＩＬ－１２组小鼠无一死亡、肺、肝、脾菌落数分别为（２２７     

Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes

The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1 cytokine profile, but none of seven Th2 clones, induced TF production and PCA. T-cell blasts from four Th1 activated clones were fixed with paraformaldehyde and added to monocytes in the presence of medium alone or their supernatants. Addition of either fixed Th1 cells or their supernatants induced low TF production (0.2 to 0.6 ng/mL), whereas addition of both resulted in much higher TF synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only interferon-gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4 ng/mL). No TF synthesis was induced by activated and fixed Th2 cells and/or their supernatants, whereas combined addition of fixed Th2 cells and Th1 supernatants or IFN-gamma induced noticeable TF production. The addition of either anti-IFN-gamma antibody or Th2 supernatants to monocytes stimulated with activated and fixed Th1 cells plus their supernatant resulted in a dose-dependent inhibition of TF synthesis, which was partially restored by neutralization of interleukin-4 (IL-4) or IL-10. Addition of recombinant IL-4, IL-13, or IL-10, but not IL-5, inhibited the Th1- induced TF production by monocytes. Data indicate that both CD8+ and CD4+ Th1, but not Th2, T cells can help TF production and PCA. Both cell-to-cell contact with activated T cells and Th1-type cytokines, in particular IFN-gamma, are required for optimal TF synthesis, whereas Th2-derived cytokines (IL-4, IL-13, and IL-10) are inhibitory. This may be of potential interest for future therapeutic strategies.