白介素-5研究进展

白细胞介素-5是白细胞介素介素家族的重要成员之一,在协调和促进以酸性粒细胞为基础的炎性过程起着关键的作用。白细胞介素-5(IL-5)及白细胞介素5受体(IL-5R)是哮喘发病的重要物质。本文对白介素-5的结构,生物学功能,及国内外相关研究作一介绍。     

白细胞介素-2及其相关药物的应用研究进展

综述白细胞介素-2及抗白细胞介素-2受体单克隆抗体的应用研究进展。白细胞介素-2是一种在机体的免疫调节中发挥着重要而复杂作用的细胞因子,既可促进淋巴细胞增殖,增强免疫功能,又能限制T细胞反应而增强机体的免疫耐受,故可用于治疗肿瘤和感染性疾病及自身免疫性疾病。     

三氧化二砷通过Bcl-2相关机制诱导哮喘患者T细胞凋亡

本研究观察了三氧化二砷对哮喘患者T细胞凋亡、白细胞介素-4分泌的影响，并探讨了Bcl-2的作用。分离哮喘患者(n＝21)和健康对照者(n＝20)的外周血T细胞，分别加入三氧化二砷和地塞米松培养24 h。用荧光显微术、流式细胞仪DNA含量分析法和细胞色素c ELISA试剂盒检测T细胞凋亡，用ELISA的方法测量血清和细胞培养上清液白细胞介素-4水平，用免疫荧光流式细胞分析法测定Bcl-2基因表达。与健康对照者比较，哮喘患者T细胞体外培养24 h后自发凋亡减慢。地塞米松使哮喘患者和健康对照者的T细胞凋亡率均增加，两试验组间增加幅度无显著差异。三氧化二砷显著增加哮喘患者T细胞凋亡率，但对健康对照者T细胞凋亡影响不明显。哮喘患者血清白细胞介素-4水平升高，T细胞Bcl-2表达上调。而且，在体外培养24 h后，哮喘患者T细胞比健康对照者T细胞自发分泌的白细胞介素-4及Bcl-2的表达水平均有所提高。三氧化二砷显著减少哮喘患者T细胞白细胞介素-4分泌，下调Bcl-2表达，但对健康对照者T细胞无明显影响。地塞米松可使两试验组T细胞释放白细胞介素-4显著减少，但对两试验组T细胞Bcl-2基因表达影响不明显。结果提示：三氧化二砷在体外可诱导哮喘患者T细胞凋亡，减少白细胞介素-4分泌，下调Bcl-2基因表达可能是其重要机制之一。     

白细胞介素-2介导体内T细胞调节功能的研究进展

白细胞介素-2(IL-2)被认为是重要的T细胞生长因子,已经用于临床,并取得一定的疗效。体内IL-2信号缺失时,却又表现为明显的自身免疫性疾病。本文就IL-2在体内介导T细胞调节功能的研究进展简单做一综述。     

IL-7及IL-15在肿瘤免疫疗法中的应用

嵌合抗原受体T细胞(CAR-T)免疫疗法经过体外将正常T细胞进行基因修饰后,再回输入患者体内,以非人类白细胞抗原(HLA)依赖性方式识别肿瘤细胞并进行杀伤。自2017年美国食品药品监督管理局(FDA)批准了诺华及Kite公司两款嵌合抗原受体T细胞产品上市以来,嵌合抗原受体T细胞疗法在全球展开蓬勃发展。白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-7(IL-7)、白细胞介素-15(IL-15)、白细胞介素-21(IL-21)等细胞因子可促使嵌合抗原受体T细胞在体外有效增殖。本文主要对白细胞介素-7及白细胞介素-15进行阐述,探讨其作用机理以及临床应用。     

白介素-2与CO2激光治疗尖锐湿疣

目的 观察白细胞介素-2与CO2激光联合治疗尖锐湿疣疗效。方法 选择尖锐湿疣36例为治疗组，予以白细胞介素-2与CO2激光联合治疗，白细胞介素-220万U，每日1次，肌肉注射，连用l0d；设对照组30例单用CO2激光治疗。结果 治疗组在减少复发率方面明显优于对照组。结论 白细胞介素-2与CO2激光联合治疗尖锐湿疣的疗效明显优于单用CO2激光治疗。     

IL-2对免疫激活和免疫耐受的双向调节作用

白细胞介素2(interleukin-2,IL-2)从被发现迄今已有30余年,但仍然是最受关注和被广泛研究的细胞因子之一。IL-2最初是从T细胞培养上清液中分离获得,并对体外培养的T细胞具有促进增殖作用,因此传统认为IL-2是一种激活T细胞,并维持T细胞分化和增殖的T细胞生长因子,同时也参与炎症或自身免疫性反应。近年来,人们在IL-2或IL-2R缺陷小鼠动物模型等的研究中发现IL-2的主要功能不仅是提升免疫反应,更重要的是维持Treg细胞的稳定及其介导的免疫耐受,故具有双向免疫调节作用,这些对IL-2生物学活性的新发现,也促使人们开始重新评价和认识临床使用IL-2的疗效、适应症和给药方式。     

免增灵对小鼠血清白细胞介素-2和肿瘤坏死因子的影响

目的研究免增灵对小鼠血清白细胞介素-2（interleukin-2，IL-2）和肿瘤坏死因子（turnout neerosisfactor，TNF-α）的影响。方法采用上海森雄科技实业有限公司生产的“小鼠白细胞介素-2定量酶联检测试荆盒”和“小鼠α-肿瘤坏死因子定量酶联检测试剂盒”测试小鼠血清中的白介素-2和α-肿瘤坏死因子。结果小鼠经环磷酰胺（化疗）后，小鼠血清的白细胞介素-2和α-肿瘤坏死因子生成减少，而免增灵可以对抗环磷酰胺的此种抑制作用，使之恢复正常。结论免增灵能改善和提高环磷酰胺降低小鼠血清白细胞介素-2和α-肿瘤坏死因子含量的功能。     

白芍总甙对白细胞介素-2产生的影响

白芍总甙(0.5～62.5mg/L)对ConA(3mg/L)诱导的大鼠脾细胞产生白细胞介素-2具有双向调节作用。同时用活化小鼠脾细胞检测了ConA诱导大鼠脾细胞产生白细胞介素-2的纯度,表明,主要以白细胞介素-2为主。     

阿尔茨海默病的调节性T细胞功能检测

目的对阿尔茨海默病（AD）患者外周血调节性T细胞功能进行研究。方法流式细胞仪测定T细胞亚群；细胞分选仪分离调节性T细胞，体外培养行淋巴细胞混合培养法检测调节性T细胞对同源／异源淋巴细胞增殖的抑制效应；ELISA法检测调节性T细胞细胞因子肿瘤坏死因子-β、白细胞介素-10的分泌水平。结果CD4^＋CD25^＋调节性T细胞细胞比例和健康对照组相比差异无显著性。肿瘤坏死因子-β、白细胞介素-10的分泌2组间差异无显著性。AD组调节性T细胞抑制功能受损，与对照组有明显差异。结论AD患者调节性T细胞抑制功能受损，可能与其接触抑制途径缺陷有关。     

Interleukin-2 in cancer

The development of recombinant interleukin-2 (rIL-2) as a treatment for cancer represented an important milestone in the development of biologic therapies. IL-2 is a natural modulator of the immune system that stimulates specialised immune system cells, namely cytotoxic T-lymphocytes (CTLs) and natural killer cells (NKCs). These cells could potentially recognise and destroy tumour cells throughout the body. However, the exact mechanism(s) by which IL-2 mediates a tumouricidal effect is not well known. Recombinant IL-2 has been primarily used in the treatment of advanced renal cell cancer (RCC) and malignant melanoma (MM). Nevertheless, the benefit of rIL-2 therapy remains very modest in these conditions. Initial results demonstrated objective response rates (shrinkage of tumour volume to less than 50%) in the 15 - 20% range with some durable responses. However, the overall response rates were lower than originally hoped for with this therapy. Moreover, the use of rIL-2 may be associated with significant side effects that could be life threatening. Despite numerous studies with rIL-2, the optimal dose and treatment schedules remain a controversial topic. To date, there are no clear immunological parameters able to predict biological response to rIL-2 administration to achieve maximum therapeutic index. In addition, combination therapy with either immunomodulators or cytotoxic drugs, is being very actively investigated.     

快速测定IL-2免疫脂质体中IL-2的含量

目的测定IL-2的含量。方法本文采用考马斯亮蓝法对IL-2靶向5-FUR前药脂质体中的IL-2进行了含量测定,在波长595nm处测定吸光度。结果试验表明IL-2含量在1～100μg/ml范围内,该法的实测值与吸光度间呈良好线性关系,稳定性、重复性均好,批内与批间试验差异无统计学意义(CV<6.6%)。结论与BCA法测定IL-2相比,考马斯亮蓝法更简便、迅速。     

IL-2基因工程菌的发酵及其包含体制备工艺的初探

本文对IL-2基因工程菌的发酵及其包含体制备工艺进行了研究.结果表明在发酵过程中pH的稳定(7.0)、糖的补充(3%)、O_2的及时供给(<10PSIG持续泵入)和发酵密度的控制(OD_(550)=1.9),对提高发酵产量至关重要(12g/L).在包含体制备及溶解工艺中,以4mol/L脲去除脂质及杂蛋白,1%SDS溶解包含体,可获最大IL_2活性单位(2.35×10~7u/ml,即相当于5L发酵可获3.53×10~9u).     

Combined Effect of Deoxynivalenol (DON) and Porcine Circovirus Type 2 (Pcv2) on Inflammatory Cytokine mRNA Expression

A host’s immune system can be invaded by mycotoxin deoxynivalenol (DON) poisoning and porcine circovirus type 2 (PCV2) infections, which affect the host’s natural immune function. Pro-inflammatory cytokines, IL-1β and IL-6, are important regulators in the process of natural immune response, which participate in inflammatory response and enhance immune-mediated tissue damage. Preliminary studies have shown that DON promotes PCV2 infection by activating the MAPK signaling pathway. Here, we explored whether the mRNA expression of IL-1β and IL-6, induced by the combination of DON and PCV2, would depend on the MAPK signaling pathway. Specific pharmacological antagonists U0126, SP600125 and SB203580, were used to inhibit the activities of ERK, JNK and p38 in the MAPK signaling pathway, respectively. Then, the mRNA expression of IL-1β and IL-6 in PK-15 cells was detected to explore the effect of the MAPK signaling pathway on IL-1β and IL-6 mRNA induced by DON and PCV2. The results showed that PK-15 cells treated with DON or PCV2 induced the mRNA expression of IL-1β and IL-6 in a time- and dose-dependent manner. The combination of DON and PCV2 has an additive effect on inducing the mRNA expression of IL-1β and IL-6. Additionally, both DON and PCV2 could induce the mRNA expression of IL-1β and IL-6 via the ERK and the p38 MAPK signal pathways, while PCV2 could induce it via the JNK signal pathway. Taken together, our results suggest that MAPKs play a contributory role in IL-1β and IL-6 mRNA expression when induced by both DON and PCV2.     

IL-2、IL-6表达与ds-DNA在SLE检测中的相关性和临床意义

目的:探讨系统性红斑狼疮(SLE)患者血清中IL-2、IL-6的表达与ds-DNA的关系。方法:用酶联免疫吸附试验(ELISA)检测40例SLE患者血清中IL-2、IL-6和抗ds-DNA抗体水平。结果:SLE患者血清IL-2水平较正常组明显降低(P<0.01),而血清中IL-6水平较正常组增高(P<0.05)。结论:在SLE患者血清中IL-6水平与ds-DNA呈正相关,对于SLE的诊断和疗效观察有重要的临床意义。     

戒毒中药玄夏对吗啡依赖大鼠戒断过程中Th1/Th2平衡的影响

目的:通过对大鼠在吗啡依赖、自然戒断和使用戒毒药玄夏治疗时Th1/Th2相关细胞因子IFN-γ、IL-2、IL-4和IL-6进行测定,以了解戒毒药玄夏对大鼠体内Th1/Th2平衡的影响。方法:成年♂SD大鼠24只,随机分配到正常对照组、吗啡依赖组、自然戒断组和玄夏治疗组,每组6只。正常对照组每日两次sc生理盐水。余3组每日sc吗啡,共8d,建立吗啡依赖模型。玄夏治疗组于给吗啡的d4起每日ig玄夏,正常对照组和吗啡依赖组于最后一次sc吗啡后取脾脏,自然戒断组和玄夏治疗组于停吗啡72h后取脾脏,制备脾细胞悬液,加入Con A后置CO2细胞培养箱中培养48h后,用酶联免疫吸附法(ELISA)测定细胞培养液中IFN-γ、IL-2、IL-4和IL-64种细胞因子的水平。结果:脾细胞培养液中,IFN-γ、IL-2和IL-6 3种细胞因子的组间差异有统计学意义(P<0.05),IL-4组间差异无统计学意义。吗啡依赖组大鼠Th1型因子IFN-γ水平显著高于正常对照组(P<0.05),IL-2的水平有升高的趋势,但差异无统计学意义;Th2型因子IL-6水平则显著低于正常对照组(P<0.05)。自然戒断组,IFN-γ的水平较吗啡依赖组有所下降,但仍显著高于正常对照组(P<0.05);IL-2的水平进一步升高,与吗啡依赖组的差异无统计学意义,但显著高于正常对照组;IL-6的水平较吗啡依赖组稍有增加。玄夏治疗组,IFN-γ水平较吗啡依赖组低,而且明显低于自然戒断组,与正常对照组的水平相似;IL-2水平较自然戒断组和吗啡依赖组低,接近正常对照组;IL-6的水平则显著低于自然戒断组(P<0.05)。结论:大鼠使用玄夏后,Th1型细胞因子IFN-γ和IL-2能恢复到正常水平,提示玄夏能抑制大鼠吗啡依赖时增强的Th1型免疫应答,对Th1/Th2平衡有调节作用。     

Interleukin-2 as immunotherapeutic in the autoimmune diseases

Interleukins, also called cytokines are secretory proteins that bind to specific receptors and play a critical role in the intercellular communication between cells of the immune system. Cytokines are mainly produced by T lymphocytes, macrophages and eosinophils. Among its functions are the activation and suppression of immune system responses, induction of cell division and regulation of memory cells. Interleukin 2 (IL-2) is a secretory monomeric glycoprotein composed of 149 amino acids containing a signal peptide of 20 amino acids. It is classified as a member of the type I cytokines family. IL-2 binds to its receptor (IL-2R receptor) with high affinity and its signaling function promotes the activation of various subtypes of lymphocytes during the process of cell differentiation to generate an immune or homeostatic response. The specificity of IL-2 depends on its binding to low, medium or high-affinity receptors. Interleukin 2 acts as a regulator of the proliferation of CD4+ and CD8+ T cells. There is a relationship between IL-2 and autoimmune diseases due to its influence in the differentiation of T helper cells, which in turn directly influence immunological response processes. Therefore, IL-2 is a key element in the control and treatment of those diseases. In recent years, many therapeutic agents based on biomolecules and recombinant chimeric proteins have been developed to treat different autoimmune diseases. In this review, we focus on the use of interleukin 2 as a versatile therapeutic agent, alone or associated with other molecules to increase the efficiency of autoimmune disease treatment.     

Cloning and sequence of guinea pig interleukin 2 (IL-2)

Interleukin 2 (IL-2) is a T-cell proliferation factor released from TH0- and TH1-type helper T-cells and is an essential cytokine for certain immune responses. We reported here cloning and sequence of IL-2 cDNA in guinea pigs, which have been used for a long time in various immunological experiments and in vivo screening tests for skin sensitization potential of chemicals. Consequently, a cDNA clone was obtained encoding guinea pig IL-2 of 520 bp in length, which contained a complete open reading frame. Alignment of the amino acid sequence with human IL-2 indicates that guinea pig IL-2 is composed of 20 amino acids (aa) of a signal peptide and 132 aa of a mature peptide with a predicted molecular weight of 15 133. Guinea pig IL-2 has an amino acid homology of 62% with human IL-2, 52% with murine IL-2, and 55% with rat IL-2. In addition, guinea pig IL-2 has a possible N-linked glycosylation site as seen in bovine and porcine IL-2. Received: 8 April 1998 / Accepted: 1 July 1998     

针药结合治疗对慢性肾小球肾炎大鼠IL-1、IL-2的影响

目的探讨针药结合治疗对实验性肾炎大鼠免疫因子IL-1、IL-2的影响。方法通过小鼠胸腺细胞增值法观察针药结合治疗对尾静脉注射小牛血清白蛋白所诱发慢性肾小球肾炎大鼠免疫因子IL-1、IL-2影响。结果针药结合治疗后,各组大鼠血清IL-1、IL-2水平明显降低,其中针药结合组,中药组与模型组比较有显著性差异（P〈0.05）。结论针药结合治疗可以抑制细胞IL-1、IL-2的释放,调节免疫,提示其作用机制可能与免疫因子调节有关。     

支气管哮喘患者外周血中IL-2﹑IL-4﹑IL-13和IgE的表达

目的：探讨哮喘患者外周血中IL-2、IL-4、IL-13和IgE的水平变化及临床意义。方法：抽取哮喘患者及正常对照组空腹静脉血2ml,采用双抗体夹心法（ELISA法）检测血清中IL-2、IL-4、IL-13和IgE的含量。结果：急性发作组和缓解组中IL-4、IL-13、IgE的含量明显高于正常对照组,差异有统计学意义（P〈0.01）,IL-2的含量低于正常对照组,差异具有统计学意义。急性发作组IL-4、IL-13、IgE高于缓解组,IL-2的含量低于缓解组,差异均具有统计学意义（P〈0.001）。结论：支气管哮喘患者外周血中IL-2、IL-4、IL-13和IgE水平的变化与支气管哮喘发病进程及临床诊治具有密切联系。