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、5d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5d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0d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.     

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 0d、3d、5d淋巴液及 0d、5d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 5d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 0d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。     

IL-6、IL-8、TNF-α与支气管哮喘血液流变性异常关系的研究

目的：探讨支气管哮喘病人血液流变性异常与血清IL-6、IL-8、TNF-α间的关系。方法：检测急性期和缓解期中、重度哮喘血液流变学指标以及血清IL-6、IL-8、TNF-α水平变化，并进行直线相关分析。结果：哮喘病人急性期全血表现粘度（WBV）、血浆粘度（ηp）、红细胞聚集指数（PAI）均明显高于缓解期和正常对照组，氧释放系数（OD）则明显低于缓解期；缓解期ηp、RAI、OD值恢复至正常水平，但WBV仍高于正常水平。哮喘急性期血清IL-6、TNF-α均显著高于缓解期和正常对照组水平，缓解期二者下降至正常水平；急性期和缓解期血清IL-8均明显高于正常对照组。急性期和缓解期血清IL-8、TNF-α与WBV呈正相关。结论：中、重度哮喘病人存在严重的血液流变学异常和细胞因子失调。IL-8、TNF-α可能参与了哮喘血液流变性异常的形成过程。     

难治性支气管哮喘淋巴液IL-6、IL-8、IL-10、IL-12检测及其意义

目前有关哮喘淋巴液中细胞因子 (ＣＫ)的变化尚未见报道。为此 ,我们检测了 31例难治性哮喘患者淋巴液中ＩＬ 6、ＩＬ 8、ＩＬ 10、ＩＬ 12水平 ,并与其血浆水平进行比较。1　材料和方法1 1　对象　哮喘组 31例 ,均为非急性发作期哮喘患者且符合全国支气管哮喘诊断标准。男 14例 ,女 17例 ,年龄 11～ 5 7岁 ,病程 5～ 35年。病情分度 :中度发作 10例 ,重度发作 2 1例 ,均经药物长期治疗无效。对照组 32例。男 17例 ,女 15例 ,年龄 2 4～ 43岁 ,均为滨州地区中心血站义务献血者。1 2　方法　本组哮喘患者均常规行胸导管引流 (ＴＤＤ )治疗。…     

重症创伤患者血清IL-6、IL-8、IL-18及TNF-α水平的变化及临床意义

目的：旨在探讨细胞因子在严重创伤后的变化及其临床意义。方法：38例创伤组患者分别设置伤后第1、3、5、7、14d五组;分别测定患者血清IL-6、IL-8、IL-18及TNF-α水平;均采用放射免疫分析。结果：创伤组患者在血清IL-6、IL-8、IL-18及TNF-α水平于伤后第1d均较对照组显著升高（P〈0.05,P〈0.01）;IL-6水平第5d开始逐渐下降,第14d下降显著,但与对照组比较仍呈显著高水平（P〈0.01）。IL-8、IL-18及TNF-α水平分别于7d及14d呈下降趋势,除IL-8已降至对照组水平外（P〉0.05）,后两项细胞因子水平依然显著高于对照组（P〈0.05,P〈0.01）。结论：动态监测患者血清细胞因子活性的变化,对于创伤程度及预后的评估,具有一定的临床意义。     

胸导管淋巴液引流对支气管哮喘血液和淋巴液流变性的影响

目的 探讨支气管哮喘血液和淋巴液流变性特点及胸导管淋巴液引流（TDD）的影响。方法 检测21例中重度哮喘TDD治疗0d、5d血液及淋巴液表观粘度，血浆粘度及淋巴上清液粘度，红细胞聚集指数（RAI）、红细胞刚性指数（TK）、氧释放系数（OD）等，并观察TDD术后缓解期哮喘病人血液流变学指标的变化。结果 哮喘病人急性期各切变率下的全血表观粘度，血浆粘度，RAI均明显高于缓解期和正常对照组，OD值则明显低于缓解期；缓解期血浆粘度，RAI，OD值恢复至正常水平，但各切变率下的全血表观粘度仍高于正常水平；TDD治疗可使哮喘病人血液粘度有所下降，哮喘病人淋巴液表观粘度，淋巴上清液粘度均明显低于其作血表观粘度和血浆粘度（相差约4-5倍和1.5倍），TDD治疗可使淋巴液粘度明显降低。结论 中重度哮喘病人存在严重的高粘滞血症，其在哮喘发病中可能起重要作用。TDD可降低哮喘病人血液，淋巴液粘度。     

支气管哮喘淋巴液与血液IL—6、IL—10、IL—12、T细胞亚群变化及胸导管引流对其的影响

诸多研究已表明哮喘与细胞因子 (ＣＫ)失调、Ｔ细胞亚群失衡等有关。目前关于哮喘病人淋巴液中ＣＫ等研究 ,国内外尚少报道。我们自 1996年 3月至 1998年 5月对 31例哮喘病人胸导管引流 (ＴＤＤ)治疗不同时间淋巴液中ＩＬ 6、ＩＬ 10、ＩＬ 12以及Ｔ细胞亚群进行了动态观察 ,现报道如下。1　对象与方法1 1　对象　选择符合全国支气管哮喘诊断标准的非急性发作期哮喘病人 31例 ,男 14例 ,女 17例 ;年龄为 11～ 57岁 ,病程 5～ 35年 ,中度发作 10例 ,重度发作 2 1例。正常对照组 32例 ,男 17例 ,女 15例 ;年龄 2 4～ 4 3岁 ,均为滨州地区中心…     

慢性湿疹患者血清IL-2、IL-8、IL-10及Gas测定

目的：探讨慢性湿疹患者血清细胞因子和胃泌素（Gas）测定的临床意义。方法：随机选择来我院皮肤科诊治的湿疹患者30例,健康检查的正常人30例,分为2组,分别测定其血清IL-2、IL-8、IL-10和Gas的含量。四项指标检测均采用放射免疫分析。结果：30例湿疹患者血清三项细胞因子水平和Gas测定结果显示,IL-2水平患者组非常显著低于对照组（P〈0.01）;IL-8水平略低于对照组,但尚无统计学意义（P〉0.05）;IL-10水平则非常显著高于对照组（P〈0.01）;Gas水平亦非常明显高于对照组（P〈0.01）。结论：血清IL-2、IL-8、IL-10和Gas水平的变化与湿疹发生有一定关系。其检测将有助于湿疹病情的动态监测及预后评估。     

人脐血多种细胞因子的含量检测及植物血凝素和脂多糖的影响

目的:通过检测人脐血血清多种细胞因子含量,观察植物血凝素(PHA)和脂多糖(LPS)的诱生影响,探讨这些细胞因子的免疫功能及移植物抗宿主病(GVHD)的发病机制。方法:采用双抗体夹心酶联免疫吸附法(ELISA),测定26份正常足月新生儿脐血及16例正常儿童外周血血清中白细胞介素4(IL-4)、IL-10、肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)、IL-12、IL-15、IL-18水平,以及PHA和LPS刺激后单个核细胞分泌上述细胞因子的诱生水平。结果:人脐血血清中IL-4的水平与正常外周血血清水平无显著差异(P＞0.05),脐血血清中IL-12的水平显著高于外周血血清(P＜0.05),其余5种细胞因子脐血血清水平均明显低于正常外周血血清水平(P＜0.05);PHA和LPS刺激后脐血单个核细胞分泌IL-4、IL-10、TNF-α、IFN-γ、IL-12、IL-15和IL-18的水平明显低于正常外周血(P＜0.05),尤以IL-4、TNF-α、IFN-γ、IL-15和IL-18非常明显。结论:脐血血清中上述细胞因子水平普遍低于正常外周血,以及脐血单个核细胞刺激后产生IL-4、IL-10、TNF-α、IFN-γ、IL-12、IL-15和IL-18等细胞因子水平的不足,表明脐血细胞免疫功能不成熟,是脐血移植后GVHD发生率低及程度轻的主要原因之一。     

肝硬化患者血清IL-6、IL-10和HA、PⅢP检测的临床意义

目的：探讨了肝硬化患者血清IL-6、IL-10和HA、PⅢP水平的变化及临床意义。方法：分别应用放免法和ELISA法对61例肝硬化患者进行了血清IL-6、IL-10和HA、PⅢP含量检测并与30名正常人作比较。结果：肝硬化患者血清IL-6、IL-10和HA、PⅢP含量均非常显著地高于正常人组（P〈0．01）,相关分析昆示,肝硬化患者血清HA、PⅢP水平与IL-6、IL-10 呈明显正相关（r=0．6216、0．5127、0＋4875、0．4715,P〈0．01）。结论：细胞因子IL-6、IL—10在肝纤维化形成中发挥重要作用,在早期肝纤维化的诊断中具有一定的临床实用价值。     

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.     

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.     

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.     

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.     

Blood leukocyte mRNA expression for IL-10, IL-1Ra, and IL-8, but not IL-6, increases after exercise.

The primary purpose of this project was to study exercise-induced leukocyte cytokine mRNA expression. Changes in plasma cytokine levels and blood leukocyte mRNA expression for interleukin-6 (IL-6), IL-8, IL- 10, and IL-1 receptor antagonist (IL-1Ra) were measured in 12 athletes following 2 h of intensive cycling ( approximately 64% Watts(max)) while ingesting a carbohydrate or placebo beverage (randomized and double blinded). Blood samples were collected 30 min preexercise and immediately and 1 h postexercise. Carbohydate compared with placebo ingestion attenuated exercise-induced changes in plasma cortisol (8.8% vs. 62%, respectively), epinephrine (-9.2% vs. 138%), IL-6 (10-fold vs. 40-fold), IL-10 (8.9-fold vs. 26-fold, and IL-1Ra (2.1-fold vs. 5.6-fold). Significant time effects were measured for blood leukocyte IL-8 (2.4-fold increase 1 h postexercise), IL-10 (2.7-fold increase), IL-1Ra (2.2-fold increase), and IL-6 (0.8-fold decrease) mRNA content, with no significant differences between Cho and Pla test conditions. In summary, gene expression for IL-8, IL-10, and IL-1Ra, but not IL-6, is increased in blood leukocytes taken from athletes following 2 h of intensive cycling and is not influenced by carbohydrate compared with placebo ingestion. mRNA expression was high enough to indicate a substantial contribution of blood leukocytes to plasma levels of IL-8, IL-10, and IL-1Ra during prolonged exercise.