细胞因子在动脉粥样硬化发生发展中的作用

细胞因子在动脉粥样硬化的发生发展中起关键性的作用.本丈综述了白细胞介素、肿瘤坏死因子、干扰素、集落刺激因子、转化生长因子和趋化因子6大细胞因子在动脉粥样硬化过程中的作用,为认识动脉粥样硬化的发生发展及治疗打下基础.     

细胞因子在抗病毒免疫中作用的研究进展

近来通过构建编码细胞因子的重组痘苗病毒（ｒＶＶ）感染不同免疫应答状态的小鼠,可以研究细胞因子在体内抗病毒免疫机理中的作用,不仅证实了ＩＦＮ－γ、ＩＮＦ、ＩＬ－２等细胞因子在抗病毒免疫中起重要作用,并对抗病毒免疫机理的传统概念提出了重要的补充与修正。     

细胞因子与自身免疫性甲状腺疾病的相关性研究进展

自身免疫性甲状腺疾病(autoimmune thyroid disease,AITD)是内分泌系统的一种常见疾病,其具体发病机制尚不明确。AITD是遗传、免疫等因素综合作用的结果。细胞因子是一类具有调节免疫反应能力的小分子蛋白质。本文主要介绍了白细胞介素、干扰素、肿瘤坏死因子与AITD发生发展的关系,综述了其参与AITD的发病机制及作为AITD预测因子的可能性,为细胞因子作为AITD的诊断途径及治疗靶点提供新思路。     

细胞因子在脑缺血中的介导作用

脑缺血后内皮细胞及其它活性细胞可分泌多种细胞因子 ,而许多细胞因子又可反作用于内皮细胞 ,破坏血脑屏障的完整性 ,进而造成脑神经损害。本文综合阐述脑缺血损害病理过程中起主要作用的细胞因子。1　白介素 - 1 ( IL- 1 )　　IL- 1可由多种活性细胞合成分泌 ,胶质细胞和内皮细胞也可合成 ,它是一类具有广泛作用的多肽。人 IL- 1分子量为 1 5～ 1 7KD,活性形式有 IL-1α、 IL - 1β、 IL - 1 rα三种形式。 IL - 1β是血浆和组织液中的主要形式 ,也是脑组织中的主要形式。它不仅能够协同其它细胞因子促进 B、T细胞活化 ,而且能够诱…     

细胞因子与类风湿关节炎的研究进展

类风湿关节炎(RA)是一种慢性、多系统的以关节的炎症损害为主要特点的自身免疫性疾病。其发病过程与多种细胞因子有关,包括TNF-α、IL-1、MMPS、IL-6、IL-17、IL-18等,这些细胞因子在RA的发病进程中起了很重要的作用,可作为治疗RA的新靶点。     

血清细胞因子变化在新生儿感染性肺炎中的诊断价值

研究IL-6、TNF-α和IL-2R在肺部感染性肺炎新生儿中的诊断价值。

收集2018年12月至2020年12月在本院妇产科出生新生儿(胎龄34~42周)资料, 根据肺部超声结果, 将新生儿分为病例组和正常组, 检测脐血中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-2受体(IL-2R), 独立样本t检验分析差异性, 多元线性回归分析IL-6、TNF-α及IL-2R与出现肺部感染的相关性, ROC曲线分析IL-6、TNF-α及IL-2R的灵敏度, VITEK-60系统鉴定病原菌。

两组一般资料剖宫产率、性别、出生体质量、胎龄等差异均无统计学意义(P > 0.05);与正常组比较, 病例组脐血炎性标志物IL-6、TNF-a、IL-2R水平均升高(P < 0.01);多元线性回归分析IL-6、TNF-a、IL-2R与新生儿出现肺部感染有关(P < 0.05);ROC曲线分析IL-6(> 155.270 pg/mL)的灵敏度为98.5%, 特异性为85.0%, 约登指数max=0.808;TNF-α(> 16.795 pg/mL)的灵敏度为89.6%, 特异性为86.7%, 约登指数max=0.763;IL-2R(> 603.935 U/mL)的灵敏度为70.8%, 特异性为86.7%, 约登指数max=0.575;病例组检出病原菌143株, 包括127例革兰阴性杆菌(肺炎克雷伯菌构成比最高, 为25.87%)和16例革兰阳性杆菌(表皮葡萄球菌构成比最高, 为2.80%)。

IL-6、TNF-α和IL-2R对肺部感染性肺炎具有识别作用, 在鉴别和预测新生儿出现感染性肺炎具有诊断价值。

     

致炎细胞因子在骨性关节炎病理生理中的作用

骨性关节炎(OA)是一种退行性病变,表现为关节软骨破坏,关节边缘骨赘形成,并伴有不同程度滑膜炎症,其病因学和发病机制还不是十分清楚。研究表明致炎细胞因子在骨性关节炎病发病的病理生理过程中起着重要的作用。本综述讨论目前关于致炎细胞因子在OA病理生理中的作用机制以及抗致炎细胞因子在治疗OA中的新进展。     

小胶质细胞生理特点及在脑缺血损伤中的作用

小胶质细胞作为中枢神经系统的免疫细胞,监测中枢神经系统微环境的变化,对微环境变化以及损伤性刺激发生快速反应。脑缺血情况下,小胶质细胞快速活化变形产生细胞毒性物质和细胞因子等,并发生一系列生物活性反应。在脑缺血的病理生理中扮演重要角色,为了探究小胶质细胞在脑缺血再灌注损伤中的作用,我们对最近几年的研究进行了综合,为以后的基础研究和临床治疗提供参考。     

TNF在疟疾感染过程中的作用

肿瘤坏死因子（ＴＮＦ）在疟疾的感染过程中有明显的双重作用。疟原虫抗原可刺激ＴＮＦ释放,ＴＮＦ反过来对疟原虫又具有杀伤和抑制作用,也同时导致多种病理改变。本着重综述了近几年ＴＮＦ在疟疾感染中作用的最新进展,探讨ＴＮＦ在疟疾感染中的利弊,为疟疾的治疗提供一定的理论依据。     

Synthesis of glycosylated human tumor necrosis factor α coupled with <Emphasis Type="Italic">N</Emphasis>-acetylneuraminic acid

In order to study the effect of glycosylation on its biological activities, and to develop TNFα with less deleterious effects, recombinant human TNFα was chemically coupled with N-acetylneuraminic acid (NeuAc). NeuAc with C9 spacer was coupled to TNFα by acyl azide method. Two glycosylated TNFαs, designated L NeuAc-TNFα and H NeuAc-TNFα, were purified by anion-exchange chromatography. NeuAc coupling to TNFα was confirmed by lectin blotting. Average number of carbohydrate molecules introduced per molecule of L NeuAc-TNFα and H NeuAc-TNFα were estimated to be 1.0 and 1.5, respectively. We examined a variety of TNFα activities in vitro, including antiproliferative or cytotoxic activities to tumor cells, proliferative effect on fibroblast cells, stimulatory effects on IL-6 production by melanoma cells and NF-κB activation in hepatoma cells. L NeuAc-TNFα and H NeuAc-TNFα exhibited reduced activities about 1/3 and 1/10 as compared to native TNFα in all the activities performed in vitro.     

微小RNA调控脓毒症患者外周血免疫因子表达及其机制研究

目的:探讨脓毒血症患者血清外周白细胞中的微小RNA(mi RNA)表达水平的变化及其在脓毒症患者中的表达意义以及免疫调控的关系。方法:采用流式细胞仪检测外周血CD4+CD25+Treg细胞表达,采用实时定量PCR(RT-PCR)方法检测110例脓毒症患者以及100例正常对照外周血白细胞中mi RNA以及Foxp3 m RNA表达量,酶联免疫吸附法测定TNF-α和IL-10浓度,序贯器官衰竭估计(SOFA)评分系统评价脓毒症患者的严重程度。对mi RNA与白细胞总数、TNF-α、IL-10和SOFA评分之间的相关性进行分析。结果:实验组mi RNA表达水平较对照组显著降低(P0.01),WBC、IL-10水平显著升高(P0.01)。实验组mi RNA表达水平以及SOFA评分、血清TNF-α和IL-10之间呈负相关关系(r值分别为-0.512、-0.623、-0.432,P0.05);与WBC无显著相关性(r=0.215,P0.05)。脓毒症患者外周血Treg表达率和Foxp3m RNA均显著高于对照组(P0.01);随病情严重而升高,轻、中、重度实验组间两两比较差异均有统计学意义(P0.01)。死亡均在重度脓毒症患者中,死亡组Treg、Foxp3 m RNA及IL-10均显著高于存活组(P0.01);mi RNA低于存活组(P0.01)。结论:脓毒症患者外周血的mi RNA表达量显著降低,表达水平在一定程度上可以反应机体的炎症反应情况,同时还可以判断疾病的严重度,且mi RNA参与对Treg细胞增殖的调节,在脓毒症免疫失衡机制中发挥一定的作用。     

Interleukin 1 and Tumor Necrosis Factor-α Stimulate the Production of Colony-Stimulating Factor 1 by Murine Astrocytes

Astrocytes have the ability to secrete colony-stimulating factor 1 (CSF-1), a growth factor known to stimulate the proliferation of brain macrophages. We have studied the effect of cytokines such as interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and interleukin 6 (IL-6) on the production of CSF-1 by cultured primary astrocytes and an astrocytic cell line derived from embryonic mouse brain. We observed that both TNF alpha and IL-1 increased CSF-1 mRNA and protein levels in the astrocytic cultures. In contrast, IL-6 was ineffective. The CSF-1 mRNA levels were strongly reduced by incubating immortalized astrocytic cells with staurosporine, a protein kinase C inhibitor, both in the absence and in the presence of cytokines. Conversely, 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator, increased CSF-1 mRNA levels. These results suggest a mechanism whereby mononuclear phagocytes could favor their own recruitment in the CNS by producing cytokines.     

重组人肿瘤坏死因子α和白细胞介素6融合基因的构建和表达

本文利用ＰＣＲ技术和基因定位突变技术,将编码人肿瘤坏死因子α（ｈＴＮＦα）和白细胞介素６（ｈＩＬ－６）成熟肽的基因通过中间接头连接成编码单一蛋白的基因,构建了融合蛋白表达载体ｐＢＩＴ,并在大肠杆菌中得到了表达。ＳＤＳ－ＰＡＧＥ的电泳胶薄层扫描显示,融合蛋白的表达量是菌体总蛋白量的２０％,其分子量约为３７ｋＤ。活性检测证实,融合蛋白既有ＴＮＦ活性,又有ＩＬ－６活性。     

Increased secretion of adrenomedullin from cultured human astrocytes by cytokines

Abstract: Adrenomedullin, originally discovered from pheochromocytoma, is a member of the calcitonin gene-related peptide family. The production and secretion of adrenomedullin by cultured human astrocytes were studied by northern blot analysis and radioimmunoassay. Northern blot analysis showed the expression of adrenomedullin mRNA in cultured human astrocytes. Immunoreactive adrenomedullin concentrations in the culture medium were 29.6 ± 1.2 fmol/10⁵ cells/24 h (mean ± SEM, n = 4). Treatment with interferon-γ (100 U/ml), tumor necrosis factor-α (1 and 10 ng/ml), or interleukin-1β (1 and 10 ng/ml) for 24 h caused >20-fold increases in immunoreactive adrenomedullin levels in the culture medium of human astrocytes. On the other hand, northern blot analysis showed only small increases (∼40%) in the adrenomedullin mRNA expression of human astrocytes with either 100 U/ml interferon-γ or 10 ng/ml interleukin-1β and no noticeable change with tumor necrosis factor-α. Reverse phase HPLC of the medium extracts of human astrocytes treated with interferon-γ, tumor necrosis factor-α, or interleukin-1β showed that most of immunoreactive adrenomedullin was eluted in the position of adrenomedullin-(1-52). On the other hand, immunoreactive adrenomedullin in the medium of human astrocytes without cytokine treatment was eluted earlier than the adrenomedullin standard, suggesting that this immunoreactive adrenomedullin represents adrenomedullin with some modifications or fragments of the adrenomedullin precursor. The present study has shown the production and secretion of adrenomedullin by human astrocytes and increased secretion of adrenomedullin by cytokines.     

<Emphasis Type="Italic">N</Emphasis>-acetylneuraminic acid coupled human recombinant TNFα exhibits enhanced anti-tumor activity against Meth-A fibrosarcoma and reduced toxicity

In order to study the effect of glycosylation on its biological activities and to develop tumor necrosis factor α (TNFα) with less deleterious effects, N-acetylneuraminic acid (NeuAc) with a C9 spacer was chemically coupled to human recombinant TNFα. NeuAc-coupled TNFα (NeuAc-TNFα) exhibited reduced activities in vitro by about threefold compared to native TNFα. In this study, we examined a variety of TNFα activities in vivo. NeuAc-TNFα reduced activities in the up-regulation of serum levels of IL-6 and NOx, but comparable activity as native TNFα in the down-regulation of the serum level of glucose. However, NeuAc-TNFα was more potent than TNFα in the up-regulation of the serum level of serum amyloid A (SAA). NeuAc-TNFα was less toxic to mice. In addition, NeuAc-TNFα exhibited an augmented anti-tumor activity against Meth-A fibrosarcoma without hemorrhagic necrosis. These results indicate that coupling with NeuAc enabled us to develop neoglycoTNFα with selective activities in vivo, including enhanced anti-tumor activity but reduced toxicity.