非小细胞肺癌患者外周血Th17细胞比例和血清IL-17水平的检测及其临床意义

目的 探讨非小细胞肺癌(NSCLC)患者外周血Th17细胞比例和自细胞介素-17(IL-17)水平的变化及其与患者临床病理的关系.方法 收集60例原发未治疗的NSCLC患者(NSCLC组)和20例健康志愿者(对照组),采用流式细胞术(FCM)检测Th17细胞比例,采用酶联免疫吸附试验(ELISA)检测血清IL-17水平.结果 NSCLC组Th17细胞占CD+3 T细胞比例高于对照组[(1.23±0.41)％比(1.05±0.28)％,t=1.679,P=0.097],鳞状细胞癌患者外周血Th17细胞比例明显高于腺癌患者[(1.31±0.39)％比(1.09±0.41)％,t=2.093,P=0.041].NSCLC组IL-17水平明显高于健康对照组[(21.11±7.87) pg/ml比(17.64±5.07)pg/ml,t=2.280,P=0.027],鳞状细胞癌患者血清IL-17表达水平明显高于腺癌患者[(23.11±8.73) pg/ml比(18.54±6.38)pg/ml,t=2.203,P=0.032].Th17细胞比例、IL-17的表达水平随临床分期的进展呈下降趋势[F=3.151,P=0.032;F=4.132,P=0.010].结论 NSCLC患者外周血中Th17细胞比例和IL-17的表达与肿瘤病理分型、TNM分期相关,可能在NSCLC的病程中发挥重要作用.     

肺癌患者Th1和Th2类细胞因子的基因检测及其与化疗的关系

目的观察肺癌患者Th1和Th2类细胞因子的基因表达与化疗的关系。方法采用逆转录聚合酶链反应(RT-PCR)技术,检测102例肺癌患者在化疗前、化疗后外周血单个核细胞(PBMC)Th1和Th2类细胞因子mRNA表达水平。结果肺癌组IL-4、IL-6和IL-10mRNA阳性表达较正常对照及良性疾病组显著增高(P≤0.001。肺癌组IFN-γ和IL-2mRNA阳性表达较正常对照及良性疾病组显著降低(P<0.05)。化疗有效组化疗后IFN-γ和IL-2mRNA阳性表达分别为42/67和43/67,较化疗前显著增高(P≤0.001;IL-4、IL-6和IL-10mRNA阳性表达分别为30/67、26/67和24/67较化疗前显著降低(P≤0.01。化疗无效组化疗前后Th1和Th2类细胞因子mRNA表达差异无统计学意义(P>0.05)。结论肺癌患者Th1类细胞因子表达受抑,Th2类因子呈强势表达;化疗可使肺癌患者Th2类细胞因子的强势表达向Th1类逆转。     

胃癌患者外周血Th17和Treg细胞的特异性转录因子与相关细胞因子的检测及临床意义

目的 了解胃癌患者外周血Th17和Treg细胞的转录因子及其相关细胞因子的表达水平,探讨其在胃癌发展进程中的作用.方法 收集57例胃癌患者、31例胃部良性疾病患者和40例健康志愿者的外周血,采用实时荧光定量逆转录聚合酶链反应(QRT-PCR)技术,检测外周血单个核细胞中Th17和Treg细胞的特异性转录因子RORγt和FoxP3 mRNA的表达水平;采用酶联免疫吸附试验(ELISA),检测胃癌患者血浆中IL-17、IL-23、转化生长因子β(TGF-β)和IL-10的浓度.结果 胃癌组FoxP3和RORγt mRNA的表达水平分别为2.349±0.491和0.794±0.304,明显高于健康对照组和良性疾病组(均P<0.05),FoxP3/RORγt比值也高于健康对照组和良性疾病组(P<0.05),而良性疾病组与健康对照组差异无统计学意义(P>0.05).中晚期胃癌组的FoxP3/RORγt比值明显高于早期胃癌组(P<0.05).胃癌组血浆中IL-17、IL-23、TGF-β和IL-10的水平明显高于健康对照组(P<0.05),中晚期胃癌组TGF-β和IL-10水平明显高于早期胃癌组(P<0.05).结论 胃癌患者存在高Th17和Treg细胞水平,且随着病程的进展Treg细胞仍维持强势,FoxP3/RORγt比值明显增高.监测胃癌患者外周血Th17和Treg细胞的特异性转录因子和相关细胞因子水平,有助于对病程的判断.     

良恶性原发肝肿瘤患者血IL-18及IL-18BP含量测定及临床意义

目的:探讨血清IL-18、IL-18BP的水平与原发性肝癌、良性肝肿瘤及肝硬化的发生、发展关东.揭示血清IL-18及IL-18BP在原发性肝癌诊断中的作用.方法:应用ELISA法检测原发性肝癌36例、良性肝肿瘤18例、肝硬化25例及正常人20例的血清IL-18及IL-18BP含量及原发性肝癌患者血中AFP的含量,比较各组间IL-18及IL-18BP含量的差别及原发性肝癌患者血AFP与IL-18、JL-18BP的关系.结果:原发性肝癌患者血清JL-18水平明显低于正常对照组、肝硬化组及良性肝肿瘤组,而血清IL-18BP的水平明显高于正常对照组、肝硬化组和良性肝肿瘤组,差异有显著性(P<0.001),且原发性肝癌组的血清IL-18及IL-18BP水平与其临床分期有密切联系:临床分期越晚,血清IL-18水平越低,血清IL-18BP水平越高;临床分期越低,血清IL-18水平越高,血清IL-18BP水平越低,差异有统计学意义(P<0.05或P<0.01).另外.原发性肝癌惠者的血清IL-18水平与AFP含量成负相关(γ=-0.715 2,n=36,P<0.01),血清IL-18BP的水平与AFP含量成正相关(γ=631 5,n=36,P<0.01);肝硬化患者、良性肝肿瘤患者血清IL-18及IL-18BP水平均明显高于正常人,差异有显著性(P<0.01).结论:外周血IL-18及IL-18BP水平可反映原发性肝癌、良性肝肿瘤及肝硬化患者的免疫功能状态及原发性肝癌患者的临床分期,可作为原发性肝癌的辅助诊断及临床分期的有效指标,与AFP同时检测,可提高原发性肝癌的诊断符合率.     

弥漫大B细胞淋巴瘤患者外周血白细胞介素6、白细胞介素8和白细胞介素10的表达及其临床意义

目的:探讨弥漫大B细胞淋巴瘤（DLBCL）患者外周血中白细胞介素6（IL-6）、白细胞介素8（IL-8）和白细胞介素10（IL-10）的表达及其临床意义。方法:回顾性分析2018年3月至2021年3月厦门大学附属第一医院78例初治DLBCL患者的临床资料，选取同期58名健康体检者作为健康对照。采用流式微球捕获芯片技术（CBA）检测受试者外周血中IL-6、IL-8和IL-10表达水平，并分析DLBCL患者这些指标与临床特征、疾病分期和预后的关系。结果:DLBCL组IL-6、IL-8和IL-10表达水平均高于健康对照组[（171.81±70.91）pg/ml比（2.71±0.28）pg/ml，（47.95±13.04）pg/ml比（3.69±0.47）pg/ml，（38.02±10.35）pg/ml比（1.77±0.23）pg/ml]，差异均有统计学意义（ t值分别为2.38、3.39、3.50，均 P<0.05）。DLBCL患者中，骨髓侵犯、国际预后指数（IPI）评分3~5分及临床分期Ⅲ~Ⅳ期患者的IL-6、IL-8和IL-10水平均高于骨髓未侵犯、IPI评分1~2分及临床分期Ⅰ~Ⅱ期患者（均 P<0.05）。DLBCL患者外周血中IL-6与IL-8、IL-6与IL-10、IL-8与IL-10表达水平均相关（ r2值分别为0.93、0.89、0.89，均 P<0.05）。IL-6、IL-8、IL-10均高表达的患者中，临床分期为Ⅲ~Ⅳ期、6个疗程后未缓解患者比例均高于IL-6、IL-8、IL-10单项及两项高表达患者，差异均有统计学意义（均 P<0.05）。 结论:DLBCL患者外周血清中IL-6、IL-8和IL-10表达水平具有较高的相关性，三者表达水平升高预示DLBCL患者疾病分期较晚、预后较差。     

肺癌患者Th1和Th2类细胞因子的基因表达及临床意义

目的观察肺癌患者体内Th1和Th2类细胞因子的基因表达及化疗对其表达的影响。方法采用逆转录聚合酶链反应（RT—PCR）技术，检测肺癌患者在化疗前、化疗后外周血单个核细胞（PBMC）Thl和Th2类细胞因子mRNA表达。结果正常对照及良性肺部疾病组Th1和Th2类细胞因子基因表达呈阴性或基本不表达；肺癌组IL4、IL．6、IL-10的mRNA表达水平显著高于良性肺部疾病组和正常对照组（P值均〈0．001）；IFN-γ无阳性表达（0／52），IL-2则仅有2例阳性表达，均较正常对照组及良性肺部疾病组明显减少（P值分别为0．006，0．007；0．004，0．003）；且Th1和Th2类细胞因子基因表达水平与肺癌的病理分型及临床分期无相关性（P值分别为0．925，0．752，0．868，0．780，0．949）。化疗后IL-4、IL-6、IL-10的阳性表达较化疗前显著减少（P值分别为0．003，0．001，0．002）。而IFN-γ、IL-2阳性表达较化疗前有显著增加（P值均〈0．001）。结论 肺癌患者Th1类细胞因子表达受抑，Th2类因子呈强势表达；化疗可使肺癌患者Th2类细胞因子的强势表达向Th1类逆转。     

非小细胞肺癌患者Th17细胞相关因子的表达及其临床意义

目的:通过检测Th17细胞及其相关因子在非小细胞肺癌（non-small cell lung cancer,NSCLC）中的表达,探讨其在NSCLC中的临床意义。方法:选择我院2016年2月至2019年2月收治的41例NSCLC患者纳为NSCLC组,选择同期在我院接受体检的健康人员19例为正常对照组（NC组）。收集NC组受检者外周血及NSCLC患者外周血、癌病灶组织和癌旁组织。采用流式细胞术检测外周血Th17细胞水平;酶联免疫吸附法检测外周血及肺组织匀浆上清液中IL-17水平;免疫组化染色法检测组织中IL-17（IL-17+细胞）水平。对比不同病理类型、病理分期NSCLC患者外周血、癌病灶组织及癌旁组织Th17、IL-17水平。结果:NSCLC组患者外周血Th17细胞及IL-17水平均高于NC组,差异有统计学意义（P<0.05）。免疫组化检测显示IL-17+细胞以细胞质呈棕黄色和（或）棕褐色为阳性表达,癌病灶组织中见典型IL-17+细胞明显散落,成团染为棕褐色。NSCLC患者癌病灶组织Th17、IL-17水平均高于癌旁组织,差异有统计学意义（P<0.05）。不同性别、年龄患者外周血Th17细胞水平差异均无统计学意义（P>0.05）。肺鳞癌和肺腺癌患者外周血Th17及癌病灶组织和癌旁组织中Th17、IL-17水平差异无统计学意义（P>0.05）。Ⅲ-Ⅳ期NSCLC患者外周血、癌病灶组织、癌旁组织Th17、IL-17水平均高于Ⅰ-Ⅱ期,差异有统计学意义（P<0.05）。结论:Th17细胞及其相关因子在NSCLC患者外周血及癌病灶组织中表达明显上调,且随着肿瘤病理分期增加显著升高,可能与NSCLC的发生发展有关。     

卵巢上皮性恶性肿瘤患者手术前后外周血Thl/Th2细胞因子表达的临床研究

目的探讨卵巢上皮性恶性肿瘤患者手术前后外周血Th1/Th2细胞因子的表达状况。方法选取2015年1月至2016年3月间复旦大学附属中山医院青浦分院收治的30例卵巢上皮性恶性肿瘤患者为癌症组,选取同期30例卵巢上皮性良性肿瘤患者为囊肿组及30例健康体检者为对照组,分别收集癌症组与囊肿组术前术后和对照组人员空腹静脉血3ml,采用酶联免疫吸附实验(ELISA)测定血清γ-干扰素(IFN-γ)和白细胞介素-4(IL-4)水平。结果术前癌症组患者IFN-γ水平低于囊肿组患者和对照组,IL-4水平高于囊肿组和对照组,Th1/Th2比值低于囊肿组和对照组,差异均有统计学意义(均P<0.05)。术后癌症组患者IFN-γ水平比术前上升,IL-4水平下降,Th1/Th2比值增加,差异均有统计学意义(均P<0.05);术前囊肿组患者与术后IFN-γ、IL-4水平及Th1/Th2比值相比,差异均无统计学意义(均P>0.05)。术后癌症组患者IFN-γ、IL-4水平及Th1/Th2比值与囊肿组患者相比,差异均无统计学意义(均P>0.05)。结论卵巢上皮性恶性肿瘤患者Th1细胞因子水平降低,Th2细胞因子水平升高,手术后得到纠正。检测恶性肿瘤患者的IFN-γ及IL-4,有助于判断恶性肿瘤预后,为免疫治疗提供参考。     

肺癌脑转移患者Th17细胞和IL-17水平变化的研究

背景与目的 Th17细胞是一种重要的辅助性T细胞,其主要分泌IL-17等细胞因子,在感染免疫、自身免疫性疾病和肿瘤免疫中均有重要意义。本研究旨在探讨Th17细胞和IL-17在肺癌脑转移患者外周血中的表达及IL-17在肺癌脑转移患者脑脊液中的表达和意义。方法流式细胞术检测22例肺癌脑转移患者和20名正常对照外周血Th17(CD3+CD4+IL-23R+)细胞的百分率,ELISA方法检测22例肺癌脑转移患者和20名正常对照血浆IL-17水平,ELISA方法检测19例肺癌脑转移患者和16例无脑转移肺癌患者脑脊液IL-17水平。结果肺癌脑转移患者外周血Th17细胞百分率(4.65%±0.72%)明显高于正常对照(2.71%±0.54%,P=0.04);其中非小细胞肺癌(non-small cell lung cancer,NSCLC)患者和小细胞肺癌(small cell lung cancer,SCLC)患者没有差异。肺癌脑转移患者血浆IL-17水平明显高于正常对照(117.4±16.43 pg/mL和72.55±8.19 pg/mL,P=0.02);其中NSCLC患者和SCLC患者没有差异。肺癌脑转移患者脑脊液IL-17水平明显高于无脑转移的肺癌患者(73.21±7.52 pg/mL和50.25±8.04 pg/mL,P=0.04)。结论肺癌脑转移患者外周血Th17细胞数量增多,血浆IL-17和脑脊液IL-17水平升高,Th17细胞和IL-17可能参与了肺癌脑转移的发生和发展。     

IL-2和IL-10在急性髓性白血病患儿血清中的水平及其临床意义

目的 观察急性髓性白血病患儿血清中白细胞介素(IL)-2和IL-10的水平及其临床意义.方法 纳入急性髓性白血病患儿80例,其中初发27例、缓解25例、复发28例.同期纳入体检健康者50例患儿为对照组.应用酶联免疫吸附法(Elisa)检测血清中IL-2和IL-10水平.结果 与对照组比较,急性髓性白血病患儿血清中IL-2水平显著降低,IL-10水平显著升高(P<0.01).血清中IL-2和IL-10水平与急性髓性白血病患儿的年龄、性别、骨髓中白血病细胞比例、FAB分型无显著相关性(P>0.05).急性髓性白血病初发和复发组患儿血清中IL-2和IL-10水平与缓解组比较,有统计学差异(P<0.01).急性髓性白血病初发与复发患儿血清中IL-2和IL-10水平比较,无统计学意义(P>0.05).结论 急性髓性白血病患儿血清中IL-2和IL-10水平变化明显,与该病的预后联系密切.     

Aggressive non-Hodgkin's lymphoma: concomitant evaluation of interleukin-2, soluble interleukin-2 receptor, interleukin-4, interleukin-6, interleukin-10 and correlation with outcome

The purpose of this study was to assess the prognostic value of a large panel of cytokines in aggressive non-Hodgkin's lymphoma (NHL) and to confront it to parameters of the International Prognostic Index (IPI). It investigated the concomitant determination of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) on a uniform population of 116 previously untreated patients. Commercially available enzyme-linked immunoassay kits were used for cytokines measurements. Results were correlated with complete remission (CR), overall survival (OS) and failure free survival (FFS). In univariate analysis, sIL-2R and IL-6 demonstrated prognostic significance for CR (p = 0.016 and p = 0.048), OS (p = 0.0011 and p = 0.0387) and FFS (p = 0.0001 and p = 0.0363), but multi-variate analysis failed to demonstrate an independent prognostic significance. In the intermediate group risk defined by IPI, patients presenting high level of sIL-2R or IL-6 demonstrated lower CR rate and survival than those with low level. In conclusion, sIL-2R and IL-6 serum levels are elevated in high grade NHL and are correlated to CR, OS and FFS, but this study did not support their independent prognostic value. However, sIL-2R and IL-6 measurements may improve risk assignment by IPI and allow a better prognostic evaluation of patients with intermediate prognosis NHL.     

IL-6和IL-6R在脑胶质瘤发病中的作用初探

目的：初步探讨ＩＬ－６和ＩＬ－６Ｒ与脑胶质瘤发生发展的关系。方法：采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）方法检测白细胞介素６（ＩＬ－６）和ＩＬ－６受体（ＩＬ－６Ｒ）基因在脑胶质瘤组织标本和正常人脑胶质细胞中的表达。结果：３０例脑胶质瘤组织标本中有２４例（８０．０％）表达ＩＬ－６、２６例（８６．７％）表达ＩＬ－６Ｒ、２２例（７３．３％）同时表达ＩＬ－６和ＩＬ－６Ｒ。人脑正常胶质细胞仅有ＩＬ－６基因弱表达,而玩ＩＬ－６Ｒ表达。结论：脑胶质瘤可能存在与肿瘤的恶性增殖有关的ＩＬ－６／ＩＬ－６Ｒ自分泌或旁分泌环路。     

Association of interleukin-1A, interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms with multiple myeloma

Interleukin-1 (IL-1) is a cytokine involved in the maturation and proliferation of B cells and plays a significant role in the development of lytic bone lesions, a major clinical feature of multiple myeloma (MM) patients. Genes that regulate products involved in the immune system are highly polymorphic and contribute to inter-individual differences that can influence the genetic predisposition and progression of particular diseases and cancers. In this study, we investigated the correlation between the single nucleotide polymorphisms IL1A -889, IL1B -511, IL1B +3954, IL1RN Mspa1 +11100 and susceptibility to MM in 74 patients and 160 controls. We found that individuals possessing IL1A -889 CT polymorphism had a higher risk in developing MM. Moreover, genotypes IL1B -511 CC, IL1B +3954 CC, IL-1RN Mspa1 +11100 CC and the combination of IL 1B +3954 CC with IL1B -511 CC or IL-1RN Mspa1 +11100 CC exerted a protective effect in individuals possessing them.     

The release of interleukin-8 during intravenous bolus treatment with interleukin-2

OBJECTIVE: To study the role that interleukin-8 might play in the activationof polymorphonuclear neutrophils during interleukin-2 therapyand the relationship of these phenomena to interleukin-2 inducedtoxicity. DESIGN: A cohort study with measurements before and after the administrationof interleukin-2. SETTING: Medical oncology department of a large teaching hospital. PATIENTS: Fourteen patients with metastatic renal cell carcinoma and 10with metastatic melanoma being treated in a phase 2 study ofthe sequential combination of interferon-Y and interleukin-2. MEASUREMENTS: Plasma levels of tumour necrosis factor-a, interleukins-6 and8 and markers of neutrophil activation (neutrophil elastaseand lactoferrin) were measured in patients receiving 5 dailyinjections of interferon-Y (100 µg/m²/day) followed by5 days of interleukin-2 (18 x 10⁶ IU/m²/day). MAIN RESULTS: Tumour necrosis factor-a rose from baseline levels of 32 (range,12 to 56) to 343 (103 to 787) pg/ml 3 hours after interleukin-2administration returning to baseline values 21 hours later.Interleukins-6 and -8 rose from baseline levels of 6 (5 to 10)and 75 (35 to 100) to 2151 (152 to 7259) and 1283 (490 to 2500)pg/ml, respectively, at 4 hours after interleukin-2 with bothreturning to baseline values by 24 hours. Peak levels of neutrophilelastase and lactoferrin, both markers of neutrophil activation,occurred 6 hours after interleukin-2 administration. CONCLUSIONS: These data indicate that following administration of interleukin-2tumour necrosis factor-a is released followed sequentially byrises in interleukins-6 and -8. It is hypothesised that theseevents result in activation of polymorphonuclear neutrophils.These activated neutrophils may play an important role in initiatingendothelial cell damage leading to the haemodynamic toxicityand the capillary leak syndrome which is typically seen followingthe administration of interleukin-2. interleukin-2, interleukin-8, renal cell carcinoma, melanoma     

Synergy of interleukin-5 with interleukin-2 in the generation of lymphokine-activated killer-cells

IL-5 synergies with IL-2 to produce increased LAK activity, although IL-5 alone induced little cytotoxic activity. The most dramatic synergy occurred with a suboptimal IL-2 concentration. The kinetics of LAK activity induced by IL-2 plus IL-5 were similar to those induced by IL-2. IL-5 exerted its effects during the late stage of IL-2 induced LAK generation. In the precursor phase, depletion of asialo-GM1+ cells preceding culture eliminated IL-2 plus IL-5 induced LAK activity. In the effector phase, IL-2 plus IL-5 induced LAK activity was eliminated by depletion of Thy1.2+ cells following culture.     

Distinctive actions of interleukin-13 and interleukin-4 on growth of hematopoietic progenitors

We examined the effects of interleukin (IL)-13 and IL-4 on growth of hematopoietic progenitors from 5-fluorouracil (5-FU)-treated mice, using an in vitro culture system. IL-13 or IL-4 alone failed to support colony formation by enriched marrow cells. IL-4 but not IL-13 in combination with IL-11 yielded a significant number of colonies. Neither IL-4 nor IL-13 affected colony formation supported by IL-3. When tested with two-factor combinations, IL-4 but not IL-13 suppressed the formation of colonies including multilineage colonies in the absence of IL-11. The inhibitory effects of IL-4 were not lineage-specific. Delayed addition experiments demonstrated that IL-4 is inhibitory in the early stage of colony formation. Effects of IL-4 on colony formation by pooled blast cells derived from 5-day culture of post-5-FU marrow cells was not evident. These findings indicate that IL-4 but not IL-13 is a negative regulator of hematopoietic progenitors, suggesting distinctive roles for IL-4 and IL-13 in early hematopoiesis.     

In vivo administration of purified human interleukin-2 to patients with cancer: development of interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors following interleukin-2 administration

Recent studies have demonstrated efficacy of immunotherapies including interleukin-2 (IL-2) in the treatment of malignancies in rodents and humans. High levels of IL-2 receptor-positive cells were found in the peripheral blood of patients receiving recombinant IL-2 in these Phase I clinical trials. This was demonstrated both in patients receiving i.v. IL-2 who had detectable circulating levels of IL-2 as well as in patients receiving i.p. IL-2 who did not. Up to 100% of the anti-Tac binding could be inhibited by preincubation with IL-2 indicating that this was indeed an IL-2 receptor that was identified. Two-color experiments demonstrated that few Leu 2-positive cells (less than 5-10%) but over 30% of the Leu 3-positive cells bore Tac antigen. Most of the M3-positive monocytes were Tac positive (83.7%) and negative for other T-cell (Leu-4) and nonspecific murine markers (Lyt-2 and Thy 1.2). Although normal individuals had a mean of only 186 units/ml (range, 83-335 units/ml) of soluble IL-2 receptor, patients receiving IL-2 had as much as 20,000 units/ml of soluble IL-2 receptor line in their serum. The physiological role of the IL-2 receptor identified on the cell surface of Leu 3 and M3-positive cells as well as in the serum is unclear. Soluble IL-2 receptors appeared in the circulation early following IL-2 administration, approximately 1 week prior to the detection of circulating IL-2 receptor-bearing cells. Further studies will be needed to assess the role of IL-2 in monocyte function, the precise function of IL-2 receptor-bearing Leu 3-positive cells, and the relationship of these findings to the toxicity and success of this immunotherapy in humans.