低氧条件下 IL-6、IL-8、IL-10作用机制研究进展

低氧(hypoxia)是机体循环血液中氧分压较低的状态,缺氧则引发机体的一系列反应。随着研究的深入,发现机体内不但存在氧化应激反应,还伴随着一系列炎症反应,IL-6、IL-8、IL-10作为常见的炎症因子也成为研究热点,本文就低氧条件下三种 IL 的作用机制作一总结,为低氧造成的机体损伤提供更多理论依据,为低氧损伤的预防及治疗提供新靶点。     

Prognostic values of IL-6, IL-8, and IL-10 in acute pancreatitis

GOALS: The prognostic importance of interleukin-6 (IL-6), IL-8, and IL-10 in the prediction of acute pancreatitis severity. BACKGROUND: Early assessment of severity in acute pancreatitis could help the patients who are at risk of developing complications. Unfortunately, the used prognostic scoring systems generally are only moderately accurate in assessing disease severity. STUDY: We studied 117 consecutive patients with a diagnosis of acute pancreatitis admitted to our hospital during the past 2 years. Laboratory parameters and cytokines were analyzed from serum taken routinely on admission. Severity criteria were noted for each patient using Ranson, Glasgow, and APACHE II scoring systems. Local and systemic complications, developed during a follow-up period, were classified by Atlanta criteria. RESULTS: IL-6 was the only parameter that statistically significantly predicted complicated acute pancreatitis (P<0.05). IL-8 and IL-10 and the 3 prognostic scoring systems used did not properly assess complicated versus noncomplicated acute pancreatitis. CONCLUSIONS: Our prospective study supported the potential importance of IL-6 in the early assessment of complicated acute pancreatitis, but also suggested that pancreatitis classified as complicated in a large number of patients could not be correctly predicted with the Ranson, Glasgow, and APACHE II scoring systems.     

醋酸盐和无醋酸碳酸氢盐血透患者外周血IL－6，TNF和淋巴细胞亚群的变化

作者系统比较了２０例血透患者应用醋酸盐和无醋酸碳酸氢盐透析液治疗前后白细胞介素－６（ＩＬ－６）、肿瘤坏死因子（ＴＮＦ）和外周血淋巴细胞亚群（ＣＤ４，ＣＤ８）的变化，结果发现：①透析后两组患者外周血ＩＬ－６均有升高，但醋酸盐组更为显著；②ＴＮＦ在醋酸盐透析后明显升高，前后差异显著（Ｐ＜０．０５），而无醋酸碳酸氢盐组改变不明显；③两组患者治疗后外周血淋巴细胞亚群（Ｃ０４／ＣＤ８比值）活性均升高，但前者以ＣＤ４的升高为主，后者以ＣＤ８的降低为主，可能具有不同的临床意义；④通过测定治疗前后β２－微球蛋白（β２－Ｍ）的水平，未发现与ＩＬ－６有直接的联系。作者认为无醋酸碳酸氢盐透析液有其独特的优点，具有临床推广应用的价值。     

白细胞介素10基因转染对小鼠心脏移植排斥反应中细胞因子表达的影响

目的 :探讨白细胞介素 10 (IL 10 )基因转染对小鼠心脏移植排斥反应中IL 12、IL 15、IL 18和IL 4表达的影响。方法 :采用小鼠颈部心脏移植模型 ,随机分为 3组 :对照组、移植组和IL 10组。于术后第 5天取移植心脏 ,用逆转录聚合酶链式反应 (RT PCR)法观察IL 12、IL 15、IL 18、IL 4及IL 10的表达情况。结果 :移植组IL 12、IL 15、IL 18表达与对照组比较明显升高 ,IL 10、IL 4表达显著降低 (均P <0 .0 1)。IL 10组IL 12、IL 15、IL 18表达与移植组比较明显降低 ,而IL 4及IL 10表达显著升高 (均P <0 .0 1)。结论 :IL 10基因转染抑制心脏移植排斥反应主要与其抑制IL 12、IL 15、IL 18等Th1型细胞因子的表达 ,促进Th2型细胞因子IL 4的表达 ,使免疫反应由Th1型向Th2型偏移有关     

IL-12及IL-10在桥本甲状腺炎发病机制中作用的研究进展

桥本甲状腺炎是一种常见的慢性自身免疫性疾病,表现为辅助性T细胞(Th)1占优势。 Th1类细胞因子白细胞介素(IL)-12表达增加,在该病的诱发及慢性迁延中起重要作用,Th2类细胞因子IL-10表达的下调也与该病有关,且随病情变化二者表达水平有所不同。因此,这些细胞因子可作为病情变化的监测指标,并且可通过调节细胞因子的表达水平从而使失衡的Th1／Th2细胞趋于平衡。这可能为桥本甲状腺炎的治疗开拓一条新途径。     

急性冠脉综合征患者血清白介素6、8、10、18水平变化及其与冠状动脉病变程度的关系研究

目的观察急性冠脉综合征(ACS)患者血清白介素(IL)6、8、10、18水平变化,探讨其与冠状动脉病变程度的关系。方法选取2012年2月—2014年9月因非特异性胸部不适而在汕头市潮阳区大峰医院接受冠状动脉造影检查患者248例,根据造影结果分为ACS组159例、稳定性心绞痛组(SA组)47例、对照组42例,其中ACS组中急性心肌梗死(AMI)患者65例(AMI组),不稳定性心绞痛(UA)患者94例(UA组)。采用酶联免疫吸附试验(ELISA)检测各组受试者血清IL-6、IL-8、IL-10、IL-18水平,并分析其与ACS患者冠状病变程度的相关性。结果 AMI、UA、SA组患者血清IL-6、IL-8、IL-18水平高于对照组,AMI、UA组高于SA组,AMI组高于UA组(P0.05);AMI、UA组患者血清IL-10水平低于对照组和SA组,UA组低于AMI组(P0.05)。159例ACS患者中单支病变29例、双支病变56例、三支病变51例、多支病变23例,不同病变支数患者血清IL-6、IL-10、IL-18水平比较,差异无统计学意义(P0.05);单支病变、双支病变、三支病变患者血清IL-8水平低于多支病变患者,单支病变患者低于三支病变患者(P0.05)。159例ACS患者中,修正的Gensini积分等级G1级24例、G2级71例、G3级36例、G4级28例,G4级患者血清IL-6水平高于G1级患者(P0.05);G2、G3、G4级患者血清IL-8、IL-18水平高于G1级患者,G3、G4级患者高于G2级患者,G4级患者高于G3级患者(P0.05);G2、G3、G4级患者血清IL-10水平低于G1级患者,G3、G4级患者低于G2级患者,G4级患者低于G3级患者(P0.05)。Spearman相关分析结果显示,血清IL-18水平与冠状动脉病变支数呈正相关(r=0.196,P0.05),而血清IL-6(r=0.013)、IL-8(r=0.019)、IL-10(r=-0.014)水平与冠状动脉病变支数均无直线相关性(P0.05);线性相关分析结果显示,血清IL-18水平与修正的Gensini积分呈正相关(r=0.261,P0.05),而血清IL-6(r=0.028)、IL-8(r=0.039)、IL-10(r=-0.022)水平与修正的Gensini积分均无直线相关性(P0.05)。结论 ACS患者存在促炎/抗炎因子失衡,监测血清IL-18水平有助于判断ACS患者冠状动脉病变程度,而IL-6、IL-8、IL-10特异性较差。     

变应性鼻炎和哮喘患者血清IL-9、IL-4、IL-5变化及临床意义

目的探讨血清IL-9、IL-4、IL-5在变应性鼻炎、支气管哮喘（哮喘）、变应性鼻炎合并哮喘中的作用。方法采用双抗体夹心ELISA法检测哮喘组、过敏性鼻炎组、过敏性鼻炎合并哮喘（合并组）患者及查体健康者（对照组）的血清IL-9、IL-4、IL-5。结果与对照组比较,三组患者的血清IL-4、IL-5、IL-9均明显升高（P均〈0．01）;其中血清IL-5合并组高于哮喘组及过敏性鼻炎组（P〈0．01,〈0．05）,过敏性鼻炎组高于哮喘组（P〈0．01）;IL-4合并组高于哮喘组（P〈0．05）。结论IL-4、IL-5、IL-9参与过敏性鼻炎和哮喘的发病,三组患者均表现为Th2型细胞因子过度表达;变应性鼻炎合并哮喘的炎症程度较高,哮喘和鼻炎也有不同炎症反应。     

DOWN-REGULATION OF FIBRINOGEN BIOSYNTHESIS BY IL-4, IL-10 AND IL-13

High levels of fibrinogen are recognized as an important vascular risk factor; however, it is not known if the increase of plasma fibrinogen is directly responsible for this risk, or is only a marker of vascular inflammation. To support this second hypothesis, Oncostatin M (OSM) is a potent stimulator of fibrinogen biosynthesis and induces smooth muscle cell proliferation. In the same way, we analysed whether interleukin-4 (IL-4), interleukin-10 (IL-10) or interleukin-13 (IL-13), which protect vessel walls from monocytes injuries leading to atherosclerosis, could influence fibrinogen biosynthesis. The two levels of regulation of fibrinogen biosynthesis were tested: firstly, the direct effect of these cytokines on fibrinogen production by the hepatoma cell line Hep G2, and secondly their effect on the secretion of hepatocyte stimulating factor (HSF) activity in the supernatant of lipopolysaccharide (LPS)-activated monocytes. IL-4 and IL-13 added to Hep G2 cells down-regulated both the increase of fibrinogen secretion induced by IL-6 and fibrinogen mRNA levels, this effect being more pronounced when Hep G2 were preincubated with the two cytokines before IL-6 addition. The effect of IL-10 was evidenced only on mRNA expression. IL-10 and IL-13 dose-dependently decrease HSF activity secreted by LPS-activated monocytes, whereas IL-4 had no effect. However, the three cytokines decreased HSF activity when monocytes were incubated with the cytokines before LPS activation. The effects of these cytokines on HSF activity are related to variations of IL-6 and OSM secretion. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since cytokines which have a protective vascular effect down-regulate fibrinogen production.     

Serum IL-4, IL-10 and IL-6 levels in inflammatory arthritis

As the available in vitro and in vivo data suggest that interleukin (IL)-4 and IL-10 have immunosuppressive activity, our hypothesis was that serum IL-4 and IL-10 levels would correlate inversely with parameters of inflammation in patients with inflammatory arthritis. IL-4 was detected in the serum of 12 out of 140 patients with rheumatoid arthritis (RA), which was increased compared to the proportion found with patients with osteoarthritis (OA; P< 0.02). In addition, IL-4 was detected in the serum of 2 of 19 patients with systemic lupus erythematosus (SLE), 2 of 24 patients with psoriatic arthritis and 1 of 5 patients with Behçet's syndrome. No IL-4 was detected in patients with the following conditions: OA (58 patients), gout (17 patients), ankylosing spondylitis (6 patients), Reiter's syndrome (6 patients), polymyalgia rheumatica (6 patients), temporal arteritis (5 patients) and scleroderma (3 patients). No IL-10 was detected in any of the sera tested. We discuss the possible relevance of these results to the regulation of the immune response evident in inflammatory arthritis.     

Function of the interleukin-2 (IL-2) receptor gamma-chain in biologic responses of X-linked severe combined immunodeficient B cells to IL-2, IL-4, IL-13, and IL-15

The interleukin-2 (IL-2) receptor gamma-chain is a common component of several members of the cytokine receptor superfamily including those for IL-2, IL-4, IL-7, IL-9, IL-15, and possibly IL-13, and has recently been renamed the common gamma-chain (gamma c-chain). Transfection experiments have shown that the gamma c-chain participates in signal transduction by IL-2, IL-4 and IL-7, but a functional role for the gamma c-chain in biological responses by normal T cells and B cells to these cytokines has not been established. In this study, we have used X- linked severe combined immunodeficiency (X-SCID) as a naturally occurring gamma c-chain gene disruption model to examine the role of the gamma c-chain in human B-cell responses to IL-2, IL-4, IL-13, and IL-15. Our experiments show that B cells from two X-SCID patients with characterized gamma c-chain gene mutations do not respond to IL-2 or IL- 15, but respond as well or better than normal B cells to both IL-4 and IL-13 in assays for B-cell activation, proliferation, and IgE secretion. This finding raises important questions about the function of the gamma c-chain in receptors for IL-4 and IL-13, and the nature of the immune defect in X-SCID.     

大肠湿热证模型大鼠血清部分白细胞介素含量的变化

目的：通过检测大肠湿热证模型大鼠血清白细胞介素-1(IL-1)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)含量的变化。探讨大肠湿热证的客观指标。方法：采用综合因素造模(饮食加气候环境加致病生物因子)复制成大肠湿热证动物模型，应用放射免疫法检测模型大鼠血清白细胞介素含量，给予清热祛湿方药急泻康治疗。观察动物模型给药后的变化。结果：该模型无论从发病条件、病变脏腑，还是主要症状、体征均近似于中医大肠湿热证型，模型大鼠血清IL-1、IL-2、IL-6含量升高，经急泻康治疗后，症状、体征及检测指标均有改善。结论：血清IL-1、IL-2、IL-6含量升高可能为大肠湿热证的客观指标。     

冠心病患者血浆IL-10,IL-17,IL-18和C反应蛋白的水平检测

目的:探讨血浆白细胞介素(IL)-10,IL-17,IL-18和C反应蛋白(CRP)在冠心病发病过程中的作用及其临床意义。方法:采用酶联免疫双抗体夹心法(ELISA)对160例冠心病患者(急性心肌梗死50例,不稳定型心绞痛68例,稳定型心绞痛42例)和40例正常人血浆中IL-10,IL-17,IL-18和CRP的水平进行检测。结果:冠心病患者血浆IL-10,IL-17,IL-18和CRP的水平均显著高于正常对照组(P<0.05)。结论:IL-10作为冠心病的保护因子,不足以阻止其发生、发展,IL-17,IL-18和CRP的水平与冠心病的发生与发展相关,其水平的检测对冠心病诊断及病情判断有重要意义。     

囊尾蚴病患者IL-4、IL-5和IL-10水平检测

目的探讨白细胞介素4(IL-4)、白细胞介素5(IL-5)和白细胞介素10(IL-10)在囊尾蚴病发病中的免疫学作用。方法用双抗体夹心(ELISA)法检测囊尾蚴病患者血清中IL-4、IL-5和IL-10水平。结果囊尾蚴病患者血清中IL-4、IL-5和IL-10水平分别为(152.3±31.2)、(256.4±23.3)和(343.9±20.8)ng/L,正常对照组血清中IL-4、IL-5和IL-10水平分别为(75.0±28.5)、(119.5±17.6)和(106.7±19.6)ng/L,2组比较差异均有统计学意义(t值分别为10.6、27.1和48.4,P<0.001)。结论囊尾蚴感染患者Th2型细胞因子表达水平失常,体液免疫功能升高,说明囊尾蚴感染可致宿主免疫功能紊乱。     

Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis

Our objective was to evaluate the levels of interleukin-6 (IL-6), soluble receptors of IL-2 (sIL-2R), IL-10, and IL-1 receptor antagonists (IL-1ra) in the serum of patients with psoriatic arthritis (PsA) and to assess the correlation between these levels and parameters of clinical activity of skin and joint disease. In total, 34 patients with PsA and ten healthy volunteers participated in the study. Assessment of joint disease included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory spinal back pain, and Schober test. Current severity of skin disease was graded according to the psoriasis area and severity index (PASI). Erythrocyte sedimentation rate (ESR) was determined as a marker of disease activity. Serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were measured by an enzyme immunoassay kit. Significantly higher serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were found in patients with PsA in comparison with healthy volunteers. A statistically significant correlation was found between levels of sIL-2R and PASI, whereas no association was found with clinical parameters of joint severity. Levels of IL-1ra correlated with the number of tender and swollen joints. No correlation was found between levels of IL-6, IL-10, and clinical parameters of skin and joint severity. In the group of patients with PsA, serum levels of sIL-2R clearly correlated with severity of skin disease, whereas levels of IL-1ra were associated with joint severity. Received: 18 June 1999 / Accepted: 1 October 1999     

Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias

 We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia. Received: November 19, 1998 / Accepted: April 9, 1999     

并殖吸虫病患者血清IL-5、IL-4、IL-13及胸腺基质淋巴细胞生成素水平检测

目的 研究并殖吸虫感染者Th2免疫应答产生的细胞因子IL-5、IL-4、IL-13、胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)的水平,筛选出可以用于临床诊断并殖吸虫病的潜在细胞因子标志物.方法 收集贵州省本地并殖吸虫病患者成年组(年龄＞18周岁)及未成年组患者(年龄≤18周岁)的血清样本各12例,以健康人血清4例为对照,ELISA检测血清中的IL-5、IL-4、IL-13、TSLP等4种细胞因子的浓度,各病例组及对照组间采用独立样本t检验分析,同时收集患者的流行病学信息.结果 成年组IL-5、IL-4、IL-13、TSLP分泌浓度分别为(19.50±5.57)pg/ml、(0.95±0.19)pg/ml、(475.30±629.81) pg/ml、(16 676.67±7 169.29) pg/ml;未成年组分别为(23.04±3.37)pg/ml、(1.05 ±0.19) pg/ml、(422.84±539.48) pg/ml、(16 242.50±6 230.81) pg/ml;对照组分别为(4.45±0.84) pg/ml、(0.32±0.12) pg/ml、(41.15±11.72) pg/ml、(490.00±123.36) pg/ml.IL-13、TSLP在成年组、未成年组患者中升高,具有统计学意义(t=1.27,P＜0.05;t=3.11,P＜0.05).在有典型并殖吸虫病流行病学特征的未成年组中,IL-5升高(t=3.11,P＜0.01),具有统计学意义;而在无典型症状的成年组中的变化无统计学意义(t=1.52,P＞0.05).IL-4在成年组、未成年组患者中均无统计学意义变化(t=1.08,P＞0.05;t=2.1,P＞0.05).结论 并殖吸虫病患者Th2免疫反应活化,IL-5、IL-13、TSLP显著上调,可以作为潜在的诊断标志物进行下一步的研究筛选.     

Human natural killer cells exposed to IL-2, IL-12, IL-18, or IL-4 differently modulate priming of naive T cells by monocyte-derived dendritic cells

Dendritic cells (DCs) play a crucial role in naive T-cell priming. Recent data suggested that natural killer (NK) cells can influence the capability of DCs to promote Th1 polarization. This regulatory function is primarily mediated by cytokines released in the microenvironment during inflammatory responses involving NK cells. In this study, we show that human NK cells exposed for short time to interleukin (IL)-12, IL-2, or IL-18, promote distinct pathways of Th1 priming. IL-12- or IL-2-conditioned NK cells induce maturation of DCs capable of priming IFN-gamma-producing Th1 cells. On the other hand, IL-18-conditioned NK cells induce Th1 polarization only when cocultured with both DCs and T cells. In this case, IL-2 released by T cells and IL-12 derived from DCs during the priming process promote interferon (IFN)-gamma production. In contrast, when NK cells are exposed to IL-4, nonpolarized T cells releasing only low levels of IL-2 are generated. Thus, the prevalence of IL-12, IL-2, IL-18, or IL-4 at inflammatory sites may differentially modulate the NK-cell interaction with DCs, leading to different outcomes in naive T-cell polarization.