癌性渗出液中IL—2,IL—6,IL—8,TNFα和IFNγ活性分析

目的与方法 应用ＥＬＩＳＡ法研究了１８例癌性渗出液（ＭＯＦ）中内源性ＩＬ－２、ＩＬ－６、ＩＬ－８、ＩＦＮγ和ＴＦＮα的生物学活性,并与恶性肿瘤病人（ＭＴＤ）血清、正常人、结核性胸膜炎（ＴＢＰ）和肝硬化病人（ＣＲＳ）进行了比较分析。结果 ＭＴＤ血清中ＩＬ－６活性高于与正常成人组（Ｐ〈０．０５）;ＩＬ－２和ＩＦＮγ活性亦低下（Ｐ〈０．５）。ＭＴＤ血清中ＩＬ－２、ＩＬ－６ＴＮＦα活性显著低于ＴＢＰ（Ｐ〉     

小剂量IL-2和IFNα与TNFα联合治疗恶性肿瘤的免疫学与临床研究

目的:研究小剂量细胞因子在恶性肿瘤免疫治疗中的意义。方法:全身应用小剂量重组干扰素(ＩＦＮα２ｂ)、白细胞介素－２(ＩＬ－２)和肿瘤坏死因子(α－ＴＮＦ)联合治疗多种恶性肿瘤６０例。应用ＡＰＡＡＰ法和免疫单向扩散法(ＲＩＤ)分析了治疗前后患者外周血中Ｔ、Ｂ淋巳细胞、ＮＫ细胞、免疫球蛋白(Ｉｇ)和补体Ｃ３活性。结果:治疗１个疗程后外周血中ＣＤ４＋的Ｔ淋巴细胞和ＣＤ２３＋的Ｂ淋巴细胞显著的高于治疗前水平(Ｐ＜０．０５);ＣＤ４＋/ＣＤ８＋比值也明显增高(Ｐ＜０．０１)。免疫球蛋白(ＩｇＭ)活性亦显著的高于治疗前水平(Ｐ＜０．０５)。ＫＰＳ积分较治疗前明显增高(Ｐ＜０．００１)。治疗后细胞因子加化疗组的ＫＰＳ积分平均增高２８．５分(Ｐ＜０．００１);ＣＲ ２６例(６５．０%);ＰＲ １１例(２７．５%),总有效率８２．５%。单纯细胞因子治疗组的ＫＰＳ积分平均增高２３分(Ｐ＜０．００１);ＰＲ １３例(６５．０%),总有效率６５．０%。结论:本方案可以显著的提高多种恶性肿瘤患者的细胞免疫和体液免疫。有可能提高肿瘤的化疗效果和患者的生存质量,延长生存期。     

小剂量IL—2和IFNα与TNFα联合治疗恶性肿瘤的免疫学与临床研究

目的研究小剂量细胞因子在恶性肿瘤免疫治疗中的意义.方法全身应用小剂量重组干扰素(IFN α 2b)、白细胞介素-2(IL-2)和肿瘤坏死因子(α TNF)联合治疗多种恶性肿瘤60例.应用APAAP法和免疫单向扩散法(RID)分析了治疗前后患者外周血中T、B淋巴细胞和NK细胞和免疫球蛋白(Ig)和补体C3活性.结果治疗1个疗程后后外周血中CD4+的T淋巴细胞和CD23+的B淋巴细胞显著的高于前水平(P<0.05);淋巴细胞和CD4+/CD8+比值也明显增高(P<0.01).KPS积分较因子加化疗前明显增高(P<0.001).免疫球蛋白(IgM)活性亦显著的高于治疗前水平(P<0.05).KPS积分较治疗前明显增高(P<0.001).治疗后细胞因子加化疗组的KPS积分平均增高28.5分(P<0.001);CR 26例(65%);PR 11例(27.5%),总有效率82.5%.单纯细胞因子治疗组的KPS积分平均增高23分(P<0.001);PR 13例(65%),总有效率65.0%.结论本方案可以显著的提高多种恶性肿瘤患者的细胞免疫和体液免疫.有可能提高肿瘤的化疗效果和患者的生存质量,延长生存期.     

Utilin's、IFNα和TNFα体外诱生免疫相关细胞因子水平的比较

目的探讨乌体林斯(Utilin′s)体外诱导正常人外周血淋巴细胞合成与分泌免疫相关细胞因子的作用.方法应用ELASA法检测Utilin′s、干扰素α(IFNα)、肿瘤坏死因子α(TNFα)培养上清中IFNγ、TNFα、IL-2、IL-6、IL-8、IL-12和IL-18的水平.结果Utilin′s培养上清中IL-8、IL-12和TNFα水平显著高于对照组(P＜0.05).Utilin′s加PHA和Utilin′s加SMMC-7721细胞抗原培养组,培养上清中7种细胞因子水平显著高于对照组(P＜0.01;P＜0.05).含有Utilin′s的3组培养上清中7种细胞因子与IFNγ、TNFα各培养组比较无显著性差异(P＞0.05).结论Utilin′s与IFNα、TNFα一样,均具有诱导和促进淋巴细胞合成与分泌免疫相关细胞因子作用.     

Utilin′s、IFNα和TNFα体外诱生免疫相关细胞因子水平的比较

目的　探讨乌体林斯 (Utilin′s)体外诱导正常人外周血淋巴细胞合成与分泌免疫相关细胞因子的作用。方法　应用ELASA法检测Utilin′s、干扰素α(IFNα)、肿瘤坏死因子α(TNFα)培养上清中IFNγ、TNFα、IL 2、IL 6、IL 8、IL 12和IL 18的水平。结果　Utilin′s培养上清中IL 8、IL 12和TNFα水平显著高于对照组 (P <0 .0 5 )。Utilin′s加PHA和Utilin′s加SMMC -772 1细胞抗原培养组 ,培养上清中 7种细胞因子水平显著高于对照组 (P <0 .0 1;P <0 .0 5 )。含有Utilin′s的 3组培养上清中 7种细胞因子与IFNγ、TNFα各培养组比较无显著性差异 (P >0 .0 5 )。结论　Utilin′s与IFNα、TNFα一样 ,均具有诱导和促进淋巴细胞合成与分泌免疫相关细胞因子作用     

肿瘤坏死因子、白细胞介素和干扰素的体内外抗鼻咽癌细胞实验研究

 目的 研究几种细胞因子对鼻咽癌细胞的抗癌效应。方法 采用鼻咽癌细胞株ＣＮＥ３，实验重组人肿瘤坏死因子（ｒｈＴＮＦα）、重组人白细胞介素２（ｒｈＩＬ－２）和干扰素γ（ＩＦＮγ）三者单独或联合应用对体外或裸鼠移植瘤的抑瘤作用。结果ｒｈＴＮＦα抑瘤作用与其浓度和用药时间呈正相关；ｒｈＴＮＦα瘤内局部注射有抑制肿瘤的生长并导致瘤块凝固性坏死；与ｒｈＩＬ－２联合增效明显；与ＩＦＮγ联合增效不明显。结论ｒｈＴＮＦα显示强力抑制ＣＮＥ３作用，ｒｈＩＬ－２有协同增强，估计在正常体内抗瘤效果更好，因有被激活的细胞免疫配合。     

白血病患者外周血IL－2、mIL－2R和TNF－α的检测及意义

４５例白血病患者，采用固相放射免疫分析法（ＲＩＡ）测定其血清白细胞介素２（ＩＬ－２）的水平，以流式细胞仪（ＦＣＭ）检测其外周血单个核细胞（ＰＭＮＣ）上膜白细胞介素２受体（ｍＩＬ－２Ｒ）的表达，用双抗体夹心ＣＥＬＩＳＡ法测定其血清肿瘤坏死固子α（ＴＮＦ－α）的含量。发现急性白血病（ＡＬ）及慢性位细胞白血病原始细胞危象（ＣＭＬ－ＢＣ）患者血清ＩＬ－２和ＴＮＦ－α的水平明显高于正常，ＣＭＬ－ＢＣ尤其急淋变者的ＰＭＮＣ上ｍＩＬ－２Ｒ阳性率较高，并与血清ＴＮＦ－α有关，而与血清ＩＬ－２无关，ｍＩＬ－２Ｒ阳性常提示白血病患者疗效差，预后不良。     

白细胞介素-6、白细胞介素-8、γ干扰素、肿瘤坏死因子-α联合检测对腹腔镜下胃癌根治术后并发肺炎的预测价值

目的 分析白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)联合检测对腹腔镜下胃癌根治术后并发肺炎的预测价值。方法 将72例胃癌患者按术后是否并发肺炎分为观察组(并发肺炎)30例和对照组(未并发肺炎)42例。比较两组患者血清IL-6、IL-8、IFN-γ、TNF-α水平,绘制受试者工作特征(ROC)曲线,分析血清IL-6、IL-8、IFN-γ、TNF-α单独及联合检测对腹腔镜下胃癌根治术后并发肺炎的预测价值。结果 观察组患者血清IL-6、IL-8、IFN-γ、TNF-α水平均明显高于对照组,差异均有统计学意义(P <0.01)。血清IL-6、IL-8、IFN-γ、TNF-α联合检测预测腹腔镜下胃癌根治术后并发肺炎的灵敏度(94.85%)高于各指标单独检测(75.12%、71.86%、69.82%、72.84%)。结论 腹腔镜下胃癌根治术后并发肺炎患者血清IL-6、IL-8、IFN-γ、TNF-α水平异常升高,联合检测可提高对肺炎的预测灵敏度,具有一定参考价值。     

肺癌患者血清sIL-2R、IL-6和TNF-α水平的测定及其临床意义

众多临床研究表明,恶性肿瘤患者存在某些细胞因子的异常改变.为了解肺癌患者血清中可溶性白细胞介素-2受体(soluble interleukin-2 receptor,sIL-2R)、白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)的水平以及它们在化疗前后的变化,本文对一组肺癌患者治疗前后外周血sIL-2R、IL-6和TNF-α进行测定,并探讨其变化及临床意义.     

全反式维甲酸对急性早幼粒细胞白血病TNF和IL-6活性的影响

目的检测急性早幼粒细胞白血病（APL）患者经过全反式维甲酸治疗后血清和白细胞胞质内肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）活性水平的变化与意义。方法TNF活性应用传统的生物学结晶紫法测定。采用IL-6依赖细胞株MH60-BSF2进行IL-6的生物学活性的测定。半固体琼脂法检测白血病集落（L-CFU）和粒一巨噬细胞系集落（GM-CFU）数量变化。结果治疗前的APL患者血清TNF和IL-6活性水平均高于对照组的相应水平（P〈0．01）。白细胞（WBC）升高期的血清TNF和IL-6活性出现降低趋势，但只有IL-6的变化具有统计学意义（P〈0．05）。完全缓解后的APL患者血清TNF和IL-6活性明显下降（P〈0．05），但仍然高于正常对照的相应水平（P〈0．05）。治疗前WBC胞质TNF和IL-6活性平均水平明显高于对照组，尤其是WBC高峰时胞质TNF活性升高更加明显（P〈0．05），缓解时胞质TNF活性明显降低。但在治疗过程中胞质IL-6活性轻度降低，没有明显的统计学意义（P〉0．05）。相关性分析结果表明，血清TNF和IL-6活性的变化与APL患者外周血WBC数量无明显相关性（P〉0．05），血清TNF变化与骨髓L-CFU数量明显相关（P〈0．05）。结论全反式维甲酸治疗虽然影响APL患者血清TNF和IL-6水平，但与该组患者的外周血WBC数量变化无线性关系。     

Analysis of changes in serum levels of TNF, IL-1 and IL-6 during administration of IL-2. Correlation with clinical response to treatment]

We have investigated the serum concentrations of TNF, IL-1 and IL-6 in 49 patients with metastatic renal carcinoma receiving interleukin 2 (IL-2) or a combination of IL-2 and interferon alpha (IFN). Our results demonstrate that IL-2 and/or IFN induce an increase of serum concentrations of IL-1 and TNF in 95% and 75% of the patients respectively. Serum IL-6 levels increase in 44% of the patients. Serum concentrations of IL-1 and TNF remain elevated 48 hours after the end of IL-2 infusion. IL-1 and TNF levels are higher in patients receiving a combination of IL-2 and IFN. TNF and IL-1 levels in serum are significantly higher in responders to IL-2 treatment 48 hours after the end of IL-2 infusion. These two biological criteria enable a subgroup of patients with a very low response rate to IL-2 to be defined. The persistent increase of these cytokines in serum indicates a persistent activation of the immune system lasting after the end of IL-2 treatment which could be involved in the antitumor response.     

白细胞介素—6及肿瘤坏死因子在食管癌组织中表达和预后的关系

目的了解白细胞介素-6（IL-6）,肿瘤坏死因子（TNF）在食管癌组织中表达和预后的关系。方法用IL-6和TNF-α的单克隆抗体对60例食管瘤组织进行免疫组织化学PAP法染色。结果随食管癌细胞分化程度的降低,IL-6和TNF-α的表达呈增强趋势。在同一细胞分化等级中,IL-6和TNF-α表达弱者的预后差于表达强者。结论食管瘤组织中IL-6和TNF-α水平的高低与食瘤预后有密切关系。     

Concentration of IL-2, IL-6, IL-8, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia after cessation of chemotherapy

The immunosuppressive effect of cytotoxic drugs, basic therapeutic agents in the treatment of childhood acute leukemias, requires monitoring of the immune system following cessation of therapy. The cytokines are soluble proteins that play a key role in the immunoregulation of the lymphocyte function. The cytokines regulate growth, differentiation and function of various cells in normal conditions. The aim of our study was to estimate serum levels of IL-2, IL-6, IL-8, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia (ALL) after cessation of chemotherapy. The study involved 150 children with ALL. This group consisted of: 30 children 1 month after treatment cessation; 30 children, 3 months later; 30 children 6 months later; 30 children, 9 months later and 30 children, 12 months later. The control group consisted of 30 healthy children. The levels of the cytokines under study were assayed using the immunoassay kits (R&D Systems, USA). During the study significant differences in TNF-alpha, IL-2 and IL-8 serum concentrations were observed among treated children and controls. However there were no differences in IL-6 and IL-10 concentrations.     

Intracavitary VEGF,bFGF, IL-8, IL-12 levels in primary and recurrent malignant glioma

Intracavitary levels of VEGF, bFGF, IL-8 and IL-12 were evaluated by ELISA in 45 patients, 7 with recurrent anaplastic astrocytoma (rAA), 12 with glioblastoma (GBM) and 26 with recurrent glioblastoma (rGBM). In 25 patients plasma levels of the molecules were also quantitated. Twenty-three healthy controls were also studied for plasma concentrations of the same molecules.Plasma levels of VEGF (mean 33.89 ± 6.71pg/ml) and bFGF (mean 11.1 ± 3.24pg/ml) were higher in patients than in controls (mean 16.78 ± 3.7pg/ml for VEGF, mean 0.21 ± 0.09pg/ml for bFGF) (p = 0.04 and p = 0.001, respectively) while plasma IL-12 levels were lower (mean 45.6 ± 1.5pg/ml in patients, mean 79.7 ± 1.3pg/ml in controls) (p = 0.009).Intracavitary VEGF levels were 5–53.307 fold higher (mean 90,900 ± 24,789pg/ml) than in the corresponding plasma. Also IL-8 concentrations were higher in intracavitary fluid (mean 6,349.76 ± 1,460.93pg/ml) than in plasma (mean 43.44 ± 24.82pg/ml). Maximum VEGF levels were found in tumor fluid of recurrent glioblastoma patients (mean 147,678 ± 39,903pg/ml), intermediate levels in glioblastoma patients (mean 20,322 ± 11,892pg/ml) and lower levels in rAA patients (mean 9,111 ± 5,789pg/ml). The data also suggest that higher intracavitary levels of VEGF and IL-8, and lower IL-12 levels, may be correlated with shorter adjunctive survival times, but more data will need to be collected to establish this correlation clearly.     

血清IL-2水平与恶性胸/腹水IL-2治疗疗效的关系

目的：对恶性胸/腹水患者血清白细胞介素2（interleukin-2,IL-2)水平进行测定，了解血清IL-2水平与胸/腹腔灌注IL-2治疗恶性胸/腹水的疗效之间的关系。以期获得判定恶性胸/腹水治疗疗效的指标。方法：88例恶性非肝癌性胸/腹水患者，均接受IL-2胸/腹腔灌注治疗，治疗前应用ELISA法检测血清IL-2水平，将IL-2测定值较高的44例患者分为一组，IL-2测定值较低的44例患者分为另一组，比较两组患者的治疗效果。结果：血清IL-2测定值较低组IL-2胸/腹腔灌注治疗的有效率为72.7%(32/44)。明显高于IL-2测定较高组的52.3%(23/44)。结论：恶性胸/腹水患者IL-2胸/腹腔灌注治疗前血清IL-2水平高低与IL-2治疗的疗效明显相关。原有IL-2水平较低的患者IL-2胸/腹腔灌注治疗的疗效较好。血清IL-2水平可作为判定IL-2胸/腹腔灌注治疗疗效的指标。     

The feasibility of monitoring NF-kappaB associated cytokines: TNF-alpha, IL-1alpha, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus

Previous investigations have demonstrated that immune activation and chronic inflammation may be one of the causes of oncogenesis. A previous study from our lab has shown significant increases of NF-kappaB dependent cytokines, TNF-alpha, IL-1alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus (OLP) patients. The aim of this analysis was to explore the potential of detecting these cytokines in whole unstimulated saliva (WUS) in monitoring the malignant transformation of OLP. Thirteen patients with OLP (with epithelial dysplasia), 13 cases with oral squamous cell carcinoma (OSCC), and 13 age-sex matched controls were enrolled in the study. The WUS samples were collected and the level of TNF-alpha, IL-1alpha, IL-6, and IL-8 in WUS was determined by ELISA. In moderate and severe dysplasia, the level of each cytokine was significantly higher than in control. In moderate dysplasia, TNF-alpha and IL-1alpha were significantly increased at a level without difference from OSCC, but IL-6 and IL-8 was detected at a concentration significantly lower than OSCC. In severe dysplasia, the level of TNF-alpha was also not significantly different from that of OSCC, and the level of IL-1alpha, IL-6, and IL-8 was still significantly lower than that of OSCC. The level of four cytokines between smokers and non-smokers in each group did not show a significant difference. These results indicate that the change of NF-kappaB dependent cytokines in WUS may in part reflect the malignant transformation of OLP and the analysis of these cytokines and may provide a useful, non-invasive surrogate endpoint for monitoring malignant transformation as well as the therapeutic response of OLP. This is the first in vivo study utilizing saliva to confirm preclinical data that NF-kappaB is upregulated in oral carcinogenesis.     

激光对荷瘤小鼠免疫系统影响的实验研究

 目的: 借助于低能量的He-Ne激光激活免疫机制, 抑制肿瘤的生长。方法: 采用双抗体夹心ELISA法及MTT法对荷瘤小鼠激光照射前后细胞因子（TL-1、IL-6、IL-8）的含量进行检测, 并对其抑制肿瘤作用进行研究。结果: 激光照射瘤鼠脾区具有促进IL-1、IL-8产生, 抑制IL-6及瘤细胞增殖的作用。与对照组相比有非常显著差异(P<0.01)。结论: 低能量激光照射具有调节患瘤鼠白细胞介素产生及抗肿瘤作用。