哮喘豚鼠IL—5,IL—3,GM—CSF mRNA表达及雷公藤内？…

目的 研究ＩＬ－５、ＩＬ－３、ＧＭ－ＣＳＦ在哮喘发病中的作用及雷公藤的干预。方法 将实验豚鼠随机分为：①哮喘组（ｎ＝８）；用卵蛋白雾化吸入诱导哮喘模型；②处理组（ｎ＝８）：用雷公藤内酯醇腹腔注射处理哮喘模型；③正常对照组（ｎ＝８）。制备ＩＬ－５、ＩＬ－３和ＧＭ－ＣＳＦ ｃＤＮＡ探针，用斑点印迹杂交法检测以上三组豚鼠支气管肺组织ＩＬ－５、ＩＬ－３和ＧＭ－ＣＳＦ ｍＲＮＡ的表达。结果 哮喘豚鼠支气管肺     

雷公藤对哮喘豚鼠外周血淋巴细胞IL-5、粒细胞-巨噬细胞集落刺激因子mRNA及CD4+、CD8+表达的影响

目的：探讨哮喘豚鼠白介素－ ５（ＩＬ－ ５） 、粒细胞－ 巨噬细胞集落刺激因子（ ＧＭ － ＣＳＦ） 及ＣＤ４ ＋ 和ＣＤ８ ＋ Ｔ 细胞在哮喘发病中的作用及雷公藤的干预作用。方法：实验分为哮喘组、雷公藤治疗组（ 处理组） 和对照组,每组各１０ 只豚鼠,采用原位杂交方法检测豚鼠外周血淋巴细胞的ＩＬ－ ５ 、ＧＭ－ ＣＳＦ ｍ ＲＮＡ 表达;应用免疫细胞化学方法检测外周血淋巴细胞ＣＤ４ ＋ 和ＣＤ８ ＋ 的表达。结果：哮喘组外周血淋巴细胞ＩＬ－ ５ 、ＧＭ－ ＣＳＦ－ ｍ ＲＮＡ 表达均明显高于处理组和对照组（ Ｐ＜ ０－０１） ,而处理组和对照组无显著差异。哮喘组外周血淋巴细胞ＣＤ４ ＋ 表达明显高于对照组和处理组（ Ｐ＜０－０１） ,ＣＤ８ ＋ 表达低于对照组和处理组（ Ｐ＜ ０－０５） 。结论：哮喘豚鼠外周血淋巴细胞ＩＬ－ ５ 、ＧＭ － ＣＳＦ ｍ ＲＮＡ 表达增高、ＣＤ４ ＋ 表达增高,ＣＤ８ ＋ 表达降低,而雷公藤甲素可降低外周血淋巴细胞ＩＬ－ ５ 、ＧＭ － ＣＳＦ ｍＲＮＡ 表达,并可提高ＣＤ８ ＋ 表达,降低ＣＤ４ ＋ 表达。表明雷公藤可能在抗哮喘气道炎症中发挥一定作用     

雷公藤对哮喘豚鼠IL-5、GM-CSF基因转录的影响及作用机制

探讨雷公藤哮喘ＩＬ－５、ＧＭ－ＣＳＦ基因转录的影响及其机制,方法：采用卵蛋白（ＯＡ）致敏复制哮喘豚鼠模型,用原位杂交就雷公藤甲素对其肺组织和外周血单个核细胞ＩＬ－５、ＧＭ－ＣＳＦｍＲＮＡ表达的影响进行检测。并通过凝胶电泳迁移试验（ＥＭＳＡ）检测ＴＰ对伴刀豆蛋白或佛波脂（ＰＭＡ）刺激的人Ｔ细胞活化蛋白－１（ＡＰ－１）的ＤＮＡ结合活性的影响。结果：①哮喘豚鼠肺组织和ＰＢＭＣ－ＩＬ－５、ＧＭ－ＣＳＦｍＲ     

加味射麻汤对哮喘豚鼠GM-CSF和ET水平的影响

用卵蛋白致敏诱发豚鼠哮喘模型,以放射免疫分析法测定经加味射麻汤治疗的动物肺组织和血浆中粒细胞－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）和内皮素（ＥＴ）含量的变化。结果表明,模型组豚鼠肺组织ＧＭ－ＣＳＦ（Ｐ〈０．０５）、ＥＴ（Ｐ〈０．００１）以及血浆中ＥＴ（Ｐ〈０．００１）含量比对照组显著升高。加味射麻汤和地塞米松均能使哮喘豚鼠肺组织中ＧＭ－ＣＳＦ、ＥＴ和血浆中ＥＴ含量下降。提示ＧＭ－ＣＳＦ和ＥＴ参与了支气管哮喘的发病机制,而加味射麻汤的作用机理与调节ＧＭ－ＣＳＦ和ＥＴ水平有关,表明该方药具有哮喘抗炎治疗的应用价值。     

rhGM—CSF／IL—3融合蛋白对人骨髓造血祖细胞体外培养的研究

研究了ｒｈＧＭ－ＣＳＦ／ＩＬ－３融合蛋白对人骨髓造血祖细胞（ＣＦＵ－ＧＭ、ＣＦＵ－ＧＥＭＭ、ＢＦＵ－Ｅ）集落形成的影响，结果表明ｒｈＧＭ－ＣＳＦ／ＩＬ－３能显著促进ＣＦＵ－ＧＭ、ＣＦＵ－ＧＥＭＭ、ＢＦＵ－Ｅ集落的形成，分别与ＧＭ－ＣＳＦ、ＩＬ－３单独或联合用药比较，差异有显著性（Ｐ〈０．００１），ＣＦＵ－ＧＭ、ＣＦＵ＝ＧＥＭＭ、ＢＦＵ－Ｅ集落的形成对融合蛋白均有剂量依赖性，培养体系浓度在５￣１０ｎ     

哮喘患者外周血单个核细胞IL-5、IL-3 mRNA表达的研究

嗜酸细胞（ＥＯＳ）是哮喘慢性炎症中的关键效应细胞。ＩＬ５、ＩＬ３能促进ＥＯＳ在骨髓的分化、成熟,使机体的ＥＯＳ产生增多,并促使ＥＯＳ在支气管肺组织的聚集及活化。哮喘患者外周血、支气管粘膜、支气管肺泡灌洗液（ＢＡＬＦ）中ＩＬ５明显升高［１］。ＩＬ３对ＥＯＳ的作用较ＩＬ５弱,它在哮喘发病机理中的作用仍有争议。本文通过对哮喘患者ＰＢＭＣＩＬ５ｍＲＮＡ、ＩＬ３ｍＲＮＡ表达水平的研究,探讨其在哮喘发病中的作用。１　材料与方法１．１　研究对象　哮喘组：哮喘患者１３例,男８例,女５例,平均年龄３…     

细胞因子在免疫复合物型肾小球肾炎发病机制中的作用

按Ｄｉｘｏｎ方法制造血清病型肾小球肾炎动物模型，进而研究其发病机制，模型ＡＥＳＳＲ血清ＣＩＣ水平明显高于正常值（Ｐ〈０．０１）；ＣＭＳＣ水平明显低于正常值（Ｐ〈０．０１），ｓＩｌ－２Ｒ，ＩＬ－８，ＩＦＮ，ＴＮＦ和ＩＬ－２水平均明显高于正常值（Ｐ〈０．０１），ＣＩＣ与ＣＭＳＣ呈高度负相关，ｒ＝－０．９４３（Ｐ〈０．０５），ＣＩＣ与ＩＬ－８呈高度正相关，相关系数ｒ＝０．８２９（Ｐ〈０．０５）。进一步证     

重组干扰素—γ对哮喘患者外周血单个核细胞IL—8和IL—10的作用研究

目的 研究重组干扰素－γ对哮喘患者体外单个核细胞ＩＬ－８和ＩＬ－１０释放的影响以及与血清ＥＣＰ水平的关系。方法 取哮喘患者８例、正常人５例的外周静脉血,分离单个核细胞培养,６６ｈ后将哮喘患者的ＰＢＭＣ上清液分为重组干扰素－γ干预组、氟美松干预组、未加干预物组,７２ｈ收集上清液测定ＩＬ－８和ＩＬ－１０的浓度。同时留取血清测ＥＣＰ。结果 哮喘者血清ＥＣＰ值与ＰＢＭＣ培养细胞上清液中ＩＬ－８值呈现显著正相关（ｒ＝０．７０１）,与ＩＬ－１０值呈显著负相关（ｒ＝０．６３８）。者喘患者血清中ＥＣＰ和ＰＢＭＣ上清液ＩＬ－８和ＩＬ－１０浓度与正常相比有显著性差异（Ｐ〈０．０５）。ｒＩＦＮ－γ干预后ＰＢＭＣ上清中ＩＬ－８较未干预组显著下降（Ｐ〈０．０５）,而ＩＬ－１０显著增高（Ｐ〈０．０５）;氟美松干预组则无明显差异性。结论 ｒ     

细胞因子与哮喘发病机理的关系

研究分设３组，哮喘发作组、哮喘缓解组和正常对照组各２０例，外周血ＩＦＮ－ｒ测定采用微量细胞病变抑制法。ＩＬ－４分泌细胞阳性率测定采用ＡＰＡＡＰ法。Ｃｏｎ－Ａ诱导Ｔｓ细胞活性测定采用Ｓｍｉｔｈ改良法。血清ＩｇＥ测定采用ＥＬＩＳＡ法。试验结果如下：（１）哮喘发作组外周血Ｔ淋巴细胞检测ＩＬ－４分泌细胞阳性率（７．６±３．５％）明显高于哮喘缓解组（３．８±２．０％），Ｐ＜０．０１，更高于正常对照组（１．８±０．５％），Ｐ＜０．０００１。在体外用ＰＨＡ诱导检测产生ＩＰＮ－Ｖ的能力，发现哮喘发作组（７３２．…     

L7212白血病小鼠IL-2活性、IL-2 mRNA表达及复方中药清毒饮对其影响的研究

目的：探讨Ｌ７２１２白血病小鼠及其受体鼠──近交系６１５小鼠ＩＬ－２活性和ＩＬ－２ｍＲＮＡ的表达及复方中药清毒饮对其影响。方法：采用ＩＬ－２依赖株ＣＴＬＬ－２及细胞原位杂交的方法检测了由ＣｏｎＡ诱导的脾细胞培养上清中ＩＬ－２活性及脾细胞ＩＬ－２ｍＲＮＡ表达。结果：发现由ＣｏｎＡ诱导的Ｌ７２１２的白血病小鼠脾细胞培养上清中ＩＬ－２活性明显低于６１５小鼠,Ｐ＜０．０５;其脾细胞中ＩＬ－２ｍＲＮＡ表达也明显低于６１５小鼠,Ｐ＜０．０１。清毒饮显著提高ＣｏｎＡ诱导的Ｌ７２１２白血病小鼠脾细胞培养上清中的ＩＬ－２活性,Ｐ＜０．００１,并能显著提高其ｍＲＮＡ表达水平,Ｐ＜０．００１。结论：清毒饮可以作为生物反应调节剂用于白血病的临床治疗。     

The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29

Cytokines are involved in virtually every aspect of immunity and inflammation. A cascade of responses evolves after cytokine activation, although optimal function might ultimately involve several complementary cytokines. Understanding the function of individual cytokines is complicated because their role can vary depending on the cellular source, target, and phase of the immune response. In fact, numerous cytokines have both proinflammatory and anti-inflammatory potential, with the contrasting outcome observed being determined by the immune cells present and their state of responsiveness to the cytokine. These issues make the study of cytokine biology daunting, particularly so for IL-10 and IL-10-related genes. The IL-10 superfamily is highly pleiotropic. These genes are linked together through genetic similarity and intron-exon gene structure. Significant commonality exists not only through shared receptors but also through conserved signaling cascades. However, its members mediate diverse activities, including immune suppression, enhanced antibacterial and antiviral immunity, antitumor activity, and promotion of self-tolerance in autoimmune diseases.     

IL-10 subfamily members: IL-19, IL-20, IL-22, IL-24 and IL-26

It has been reported that the CD4+ T cell is a very important source of interleukin 10 (IL-10), while CD8+ cells produce low amounts. IL-10 exerts several immune stimulating, as well as inhibitory effects. There are at least five novel human IL-10 family-related molecules: IL-19, IL-20, IL-22, IL-24, and IL-26. Activated T cells produce IL-19, IL-22 and IL-26, while IL-24 is produced by activated monocytes and T-cells. IL-20 induces cheratin proliferation and Stat-3 signal transduction pathway, while IL-22 induces acute-phase production by hepatocytes and neonatal lethality with skin abnormalities reminiscent of psoriasic lesions in humans. In addition, IL-22 mediates inflammation and binds class II cytokine receptor heterodimers IL-22 RA1/CRF2-4. This cytokine is also involved in immuno-regulatory responses. IL-26 (AK155) is a novel cytokine generated by memory cells and is involved in the transformed phenotype of human T cells after infection by herpes virus. All these new IL-10 subfamily member cytokines are strongly involved in immune regulation and inflammatory responses.     

Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-gamma genes in the Korean population

Cytokines play a crucial role in regulating the immune and inflammatory responses. The collective influence of several cytokines can regulate immune responses as complex as those underlying allograft rejections or autoimmune diseases. Polymorphisms in the regulatory regions of the cytokine genes may influence their expression. Therefore, the polymorphisms of cytokine genes are potentially important as genetic predictors of the disease susceptibility or clinical outcome. In 311 unrelated healthy Korean individuals, we investigated the polymorphisms of cytokine genes (interleukin-1 [IL-1], IL-2, IL-4, IL-6, IL-10, and interferon-gamma [IFN-gamma]), which had been previously reported to be associated with a number of immune diseases, transplant complications, and direct or indirect influences on the level of expression and production. And we also compared the results to those published for other populations. The genotype distributions were consistent with the assumption of the Hardy-Weinberg equilibrium, with the exceptions of IL-1B +3954 and IL-6-174 polymorphisms. The polymorphisms examined in this study were almost similar to that observed in Asian populations. There were significant differences of the polymorphisms, except for IL-4 receptor alpha +1902, between Korean and other populations. Comparing the alleles associated with higher level of expression and production, IL-1B +3954*T, IL-2-330*G, and IL-4-590*T alleles were significantly higher, and IL-1RN*A2, IL-10-1082*G, and IFN-gamma*2 alleles were lower in Koreans than other populations. Especially in IL-6 promoter -174 polymorphism, we found only the G allele associated with higher plasma IL-6 levels. In haplotype analysis of IL-10 promoter polymorphisms, the GCC haplotype, associated with higher expression of IL-10, was significantly lower in Koreans. These results may be helpful for understanding transplant-related complications, immune or autoimmune diseases, and malignant diseases in the Korean population.     

IL-1, IL-18, and IL-33 families of cytokines

Summary: The interleukin-1 (IL-1), IL-18, and IL-33 families of cytokines are related by mechanism of origin, receptor structure, and signal transduction pathways utilized. All three cytokines are synthesized as precursor molecules and cleaved by the enzyme caspase-1 before or during release from the cell. The NALP-3 inflammasome is of crucial importance in generating active caspase-1. The IL-1 family contains two agonists, IL-1α and IL-1β, a specific inhibitor, IL-1 receptor antagonist (IL-1Ra), and two receptors, the biologically active type IL-1R and inactive type II IL-1R. Both IL-1RI and IL-33R utilize the same interacting accessory protein (IL-1RAcP). The balance between IL-1 and IL-1Ra is important in preventing disease in various organs, and excess production of IL-1 has been implicated in many human diseases. The IL-18 family also contains a specific inhibitor, the IL-18-binding protein (IL-18BP), which binds IL-18 in the fluid phase. The IL-18 receptor is similar to the IL-1 receptor complex, including a single ligand-binding chain and a different interacting accessory protein. IL-18 provides an important link between the innate and adaptive immune responses. Newly described IL-33 binds to the orphan IL-1 family receptor T1/ST2 and stimulates T-helper 2 responses as well as mast cells.     

支气管哮喘病人胸导管淋巴液与血清IL-6、IL-8、 IL-10、IL-12、TNF-α水平的对比研究

目的：探讨哮喘病人胸导管淋巴液和血清IL-6、IL-8、IL-10、IL-12及TNF-α水平变化。方法：采用酶联免疫吸附试验（ELISA）检测31例行胸导管引流治疗的中、重度哮喘病人术后0 d、3 d、5 d淋巴液及0 d、5 d血清IL-6、IL-8、IL-10、IL-12以及TNF-α水平。结果：哮喘病人胸导管引流淋巴液中IL-6、IL-8、IL-10、TNF-α水平均高于正常对照组血清水平，而IL-12则明显低于正常血清水平；引流5 d淋巴液中IL-6、IL-8、IL-10及TNF-α明显低于，IL-12则显著高于引流0 d时水平；同时哮喘病人血清IL-10、TNF-α含量低于，血清IL-12则高达正常对照组水平。结论：哮喘病人淋巴液中存在以IL-12产生受抑和炎性细胞因子产生亢进为特征的细胞因子失调，且淋巴液中CK变化与血清变化大致平行。     

Ovarian follicular concentration of IL-12, IL-15, IL-18 and p40 subunit of IL-12 and IL-23

BACKGROUND: The aim of the study was to determine the presence of interleukin (IL)-12, IL-15, IL-18 and p40 subunit of IL-12/IL-23 in follicular fluid from spontaneous cycles and the relation between the concentration of selected cytokines and IVF-embryo transfer outcome. METHODS: IVF-embryo transfer and enzyme immunoassay (EIA) (R&D Systems, Minneapolis, MN, USA and MBL, Nagoya, Japan) were used. RESULTS: Follicular fluid of women included in the IVF-embryo transfer procedure contained common p40 subunit of IL-12/IL-23 (median 70.1 pg/ml), IL-15 (median 1.3 pg/ml) and IL-18 (median 38.2 pg/ml). There was a significant negative correlation between follicular fluid concentrations of IL-15 and IL-18 (R=-0.392, P=0.003). Significantly higher concentrations of common p40 subunit of IL-12/IL-23 (median 79.8 pg/ml) were found in the follicular fluid taken from follicles containing oocytes, when compared with those without an oocyte (median 44.5 pg/ml, P=0.006). Patients who achieved clinical pregnancy had significantly decreased concentration of IL-15 (median 0.8 pg/ml) compared with patients without successful IVF-embryo transfer outcome (median 1.4 pg/ml, P=0.047). CONCLUSION: Follicular fluid collected from spontaneous cycles contains detectable levels of p40 subunit of IL-12/IL-23, IL-15 and IL-18. Increased concentrations of p40 subunit of IL-12/IL-23 in follicles containing oocytes suggest an important role of this cytokine in reproduction. Possible negative value of IL-15 as a predictor of IVF-embryo transfer success remains to be determined.     

Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma

Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon-gamma (IFN-gamma) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228.35 versus 138.72 pg/ml, P < 0.001; IL-12: 0.00 versus 0.00 pg/ml, P = 0.001; IL-10: 2.51 versus 0.05 pg/ml, P < 0.034; IL-13: 119.38 versus 17.89 pg/ml, P < 0.001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22.40 versus 11.86 pg/ml and 3.42 versus 0.61 pg/ml, respectively), although the differences were not statistically significant (P = 0.077 and 0.053, respectively). The percentage of IFN-gamma-producing Th cells was significantly higher in normal control subjects than asthmatic patients (23.46 versus 5.72%, P < 0.001) but the percentage of IL-4 producing Th cells did not differ (0.72 versus 0.79%, P > 0.05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29.6 versus 8.38%, P < 0.001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma.     

Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26

The family of IL-10-related cytokines includes several human members, IL-19, IL-20, IL-22, IL-24 and IL-26, and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival ad expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA(+) T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles. After three to four cycles of stimulation, IL-10 and CMV-IL-10 led to increased IFN-gamma and IL-10 but decreased IL-4 and IL-13. Interestingly, long-term exposure of T cells to IL-19, IL-20 and IL-22 down-regulated IFN-gamma but up-regulated IL-4 and IL-13 in T cells and supported the polarization of naive T cells to Th2-like cells. In contrast, neutralization of endogenous IL-22 activity by IL-22-binding protein decreased IL-4, IL-13 and IFN-gamma synthesis. The antigen-specific suppressor activity of IL-10 and CMV-IL-10 was not observed for any of the other IL-10-family cytokines. These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles.     

Blood Serum Levels of IL-2, IL-6, IL-8, TNF-α and IL-1β in Patients on Maintenance Hemodialysis

Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure (CRF) commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis (HD) session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid, complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4±2.9 years, on regular HD maintenance therapy for mean 68±10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8 and TNF-αin CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein (CRP) as an additional parameter. CRP concentration was increased in HD patients when compared with healthy controls. The concentrations of IL-1, IL-6, IL-8 and TNF-αwere increased, whereas the serum level of IL-2 was not altered during a single HD session.