白细胞介素-10基因多态性和自身免疫性疾病的相关性研究

白细胞介素-10(IL-10)是一种多功能的细胞因子,它能抑制T helper1细胞(Th1细胞)产生γ-干扰素(IFN-γ),故最初被定义为细胞因子合成抑制因子(CSIF),主要由T helper 2细胞(Th2细胞)合成。自身免疫性疾病是由机体免疫效应细胞或免疫效应分子针对自身组织或细胞产生免疫应答,最终导致组织损伤或器官功能障碍的炎症性疾病,发病率占世界人口     

白细胞介素17在类风湿关节炎患者外周血中的表达

类风湿性关节炎（RA）是以关节滑膜炎症为主要表现的自身免疫性疾病。随着近年来对CD4^＋效应性T细胞功能性亚群研究的深入，发现其新亚群辅助性T淋巴细胞17（Th17）在自身免疫病发病机制中具有重要的作用。作为Th17亚群的主要效应细胞因子，白细胞介素17（IL-17）在RA疾病发生、发展中的角色成为RA研究的热点。     

白细胞介素-35在血液系统疾病免疫逃逸中的研究现状

白细胞介素(IL)-35是最新发现的IL-12细胞因子家族成员之一, 是免疫抑制性细胞因子, 主要由调节性T细胞(Treg)和调节性B细胞(Breg)产生, 其诱导肿瘤细胞逃避免疫识别与清除, 从而促进肿瘤的发生、发展。IL-35在多种血液系统疾病患者中高表达, 由于其免疫抑制作用, IL-35逐步成为近年相关研究热点, 并为研究疾病的免疫抑制治疗提供新思路。笔者拟就IL-35在血液系统疾病免疫逃逸中作用的研究现状进行阐述, 旨在为其在血液系统疾病的诊疗及预后评估中的应用提供理论参考。     

手足口病患儿Th17/Treg及其相关细胞因子的临床意义

目的探讨外周血辅助性T细胞17(Th17)与调节性T细胞(Treg),血清中相关细胞因子白细胞介素-17(IL-17)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、转化生长因子-β(TGF-β)在手足口病(HFMD)中的作用。方法选取125例HFMD急性期患儿和45例健康体检者,其中急性期HFMD患儿分为普通组(69例)和重症组(56例)。外周血Th17、Treg百分数检测采用流式细胞术,血清IL-17、IL-6、IL-10、TGF-β水平检测利用酶联免疫吸附试验测定。结果和对照组相比,重症组和普通组患儿外周血Th17百分比和Th17/Treg比值,以及血清IL-17、IL-6水平均升高(均P0.05),外周血Treg百分比和血清IL-10、TGF-β水平均降低(均P0.05)。重症组患儿外周血Th17百分比和Th17/Treg比值,以及血清IL-17、IL-6水平均高于普通组(均P0.05),外周血Treg百分比和血清IL-10、TGF-β水平均低于普通组(均P0.05)。结论 Th17和Treg及其相关细胞因子水平变化异常与HFMD发病及疾病进程相关。     

白细胞介素-27研究进展

细胞因子介导的免疫反应在许多疾病的发病机制中均发挥着关键性作用。白细胞介素-27（IL-27）是近期新发现的隶属于IL-6/IL-12家族的细胞因子,它通过不同的作用机制参与自身免疫性疾病、炎症及肿瘤等多种疾病的发生、发展及转归。许多研究证明,在缺乏IL-27的免疫疾病中,多种炎症因子高表达,从而产生严重的炎症反应。然而,IL-27还能促进Th1细胞的分化,具有一定的促炎作用。因此,IL-27具有免疫抑制和促炎双重作用。本文主要从IL-27在自身免疫性疾病、感染和肿瘤等疾病中发挥的作用及近期研究进展方面加以阐述。     

白细胞介素-12家族在肉芽肿相关疾病中的研究进展

正肉芽肿可定义为巨噬细胞及其衍生细胞(如上皮样细胞、多核巨细胞、T细胞及B细胞)的聚集,伴随或不伴随其他炎症细胞的出现。新近研究发现白细胞介素-12(IL-12)家族与肉芽肿的发生、发展有着密切的联系。本文就IL-12家族与肉芽肿相关疾病作一综述,为揭示和研究以IL-12家族为靶点的肉芽肿性疾病诊断、治疗及预后奠定基础。1 IL-12家族IL-12家族包括IL-12、IL-23、IL-27和IL-35,是一类由异     

白细胞介素-23的研究进展

白细胞介素-23(IL-23)是造血细胞因子家族成员,它是由p19和p40两个亚基组成的活性复合体,IL-23受体由IL-12β1和IL-23R构成,IL-23的信号途径与白细胞介素-12(IL-12)有相同的Jak-Stat信号分子,IL-23的功能与IL-12也存在许多相同之处,但也有其独特的功能。IL-23可作用于活化的T细胞、记忆性T细胞和树突状细胞,产生γ干扰素(IFN-γ)和IL-12等细胞因子,在炎症性疾病、自身免疫性疾病的发病以及抗肿瘤和抗感染等方面发挥重要作用,有望成为新的免疫治疗因子。     

习惯性流产患者绒毛和蜕膜中Treg/Th17免疫失衡的检测及其临床意义

目的探讨绒毛和蜕膜中调节性T细胞(Treg)/Th17免疫失衡在习惯性流产(RSA)患者免疫发病机制中的作用。方法收集RSA患者和自愿终止妊娠的早孕妇女(正常对照组)的绒毛和蜕膜,采用流式细胞术检测其中Treg和Th17细胞数量,采用RT-PCR检测其中叉头翼状螺旋转录因子(Foxp3)和维甲酸相关核孤儿受体γt(RORγt)的mRNA水平;收集RSA患者和正常对照组的外周血,采用酶联免疫吸附试验(ELISA)检测其中转化生长因子-β(TGF-β)、白细胞介素(IL)-10、IL-17A和IL-17F的水平;统计分析Treg细胞和其相关细胞因子、Th17细胞和其相关细胞因子之间的相关性。结果和正常对照组比较,RSA患者绒毛和蜕膜中Th17细胞明显增多(均P0.01),Treg细胞明显减少(均P0.01),RORγt的mRNA水平明显升高(均P0.01),Foxp3的mRNA水平明显降低(均P0.01);RSA患者外周血中IL-17A和IL-17F水平明显升高(均P0.01),TGF-β和IL-10水平明显降低(均P0.01);RSA患者和正常对照组Treg细胞数量和TGF-β及IL-10水平、Th17细胞数量和IL-17A及IL-17F水平均呈正相关(均P0.01)。结论绒毛和蜕膜中Treg/Th17免疫失衡可能与RSA的免疫发病机制有关。     

白细胞介素-10和白细胞介素-12在丙型肝炎病毒感染中的作用

丙型肝炎病毒(HCV)感染是慢性肝病、肝细胞癌的主要病因。目前,有关丙型肝炎发病的具体机制仍未明确,但多项研究证实,CD4+T细胞应答与肝细胞的损伤和HCV感染的结局密切相关。IL-12、IL-10是CD4+T细胞Th1型、Th2型细胞免疫的代表性细胞因子,在HCV感染过程中发挥了特殊作用。该文就IL-10、IL-12在HCV感染中的作用的相关研究进行综述。     

多发性硬化与白细胞介素的关系

多发性硬化(MS)是一种原发于中枢神经系统的自身免疫性疾病,其确切的发病机制尚不清楚。辅助性T细胞(Th)1被认为是MS的主要致病性T细胞。由Th1细胞分泌的白细胞介素(IL)-12可刺激T细胞和自然杀伤细胞,进一步加重炎症反应。IL-23、IL-27、IL-17和IL-10在MS的发病中也起重要作用。本文即对上述IL与MS关系的研究进展进行综述。     

Helicobacter pylori infection enhances mucosal interleukin-1β, interleukin-6, and the soluble receptor of interleukin-2

It is thought thatHelicobacter pylori colonization of the gastric mucosa might stimulate the production of several cytokines, which might trigger and maintain the gastric inflammation associated withHelicobacter pylori infection. In the present study we evaluated interleukin-1β, interleukin-6, and the soluble receptor of interleukin-2 both in mucosal homogenates and in the sera ofHelicobacter pylori-infected (39 cases) and uninfected (40 cases) patients to investigate whether there was any relationship between variations in cytokines and (1) the severity ofHelicobacter pylori-associated gastritis or (2) CagA-positiveHelicobacter pylori strains. Mucosal, but not serum levels of interleukins-1 and-6 and interleukin-2 receptor were significantly higher in infected than uninfected patients, Serum levels ofHelicobacter pylori antibodies were significantly higher in infected than uninfected patients, These levels correlated with mucosal interleukin-1β. The degree of antral or body inflammatory grade was higher in infected than in uninfected patients; cytokines levels were higher in patients with high-grade gastritis, most of whom wereHelicobacter pylori positive. Patients infected with CagA-positive strains also had higher levels of interleukin-1β, but not of interleukin-2 receptor or interleukin-6. In conclusion,Helicobacter pylori infection results in a local increase in interleukins-1β and-6 and interleukin-2 receptor associated with high-grade mucosal inflammation. Interleukin-1β seems to favor anti-Helicobacter pylori antibody production, and mucosal levels are enhanced mainly in patients infected with cytotoxicHelicobacter pylori strains.     

Blocking interleukin-1 receptors

Summary During inflammation, injury, immunological challenge or infection, interleukin-1 appears to mediate, in part, the pathogenesis, of disease. Most studies on interleukin-1 are derived from experiments in which bacterial products, such as endotoxins from Gram-negative bacteria or exotoxins from Gram-positive organisms, are used to stimulate macrophagic cells. In general, several cytokines are induced by microbes to their products. Although cytokines are thought to play a role in the outcome of disease, only a few have been directly implicated as mediators of the pathogenic mechanisms of the host. Studies on specific inhibition of interleukin-1 activity have employed interleukin-1 receptor antagonist, interleukin-1 receptors blocking antibodies or soluble interleukin-1 receptors. Experiments in vitro, in animal models of disease and in human subjects have shed considerable light on a critical role for interleukin-1 in the pathogenesis of disease. This review focuses on interleukin-1 as a cytokine of strategic importance to the outcome of disease, particularly inflammatory and infectious diseases.     

Interferon-gamma differentially regulates interleukin-12 and interleukin-10 production in leprosy.

The ability of monocytes to influence the nature of the T cell response to microbial pathogens is mediated in part by the release of cytokines. Of particular importance is the release of IL-12 and IL-10 by cells of the monocyte/macrophage lineage upon encountering the infectious agent. IL-12 promotes cell mediated immunity (CMI) to intracellular pathogens by augmenting T-helper type 1 responses, whereas IL-10 downregulates these responses. The ability of IFN-gamma to modulate the balance between IL-12 and IL-10 production was examined by studying leprosy as a model. In response to Mycobacterium leprae stimulation, IFN-gamma differentially regulated IL-12 and IL-10 production resulting in upregulation of IL-12 release and downregulation of IL-10 release. Furthermore, we determined that the mechanism by which IFN-gamma downregulates IL-10 was through the induction of IL-12. The data suggest a model of lymphocyte-monocyte interaction whereby the relative presence or absence of IFN-gamma in the local microenvironment is a key determinant of the type of monocyte cytokine response, and hence the degree of CMI in the host response to infection.     

烧伤患者血浆白介素-8和白介素-10水平的变化

目的：观察严重烧伤患者血浆白介素 ８（ＩＬ ８）和ＩＬ １０ 水平的变化,探讨其与烧伤后全身感染的关系。方法：收集１９ 例严重烧伤患者的血浆,利用酶联免疫吸附（ＥＬＩＳＡ）法测定血浆中ＩＬ ８ 和ＩＬ １０ 水平。结果：烧伤后患者血浆ＩＬ ８ 和ＩＬ １０ 水平急剧升高;非脓毒症患者血浆ＩＬ ８ 和ＩＬ １０ 水平在伤后逐渐降至正常,而脓毒症组患者则急剧升高。３ 例死于脓毒症者血浆ＩＬ ８ 和ＩＬ １０ 持续在高水平状态。结论：烧伤能诱导机体产生ＩＬ ８ 和ＩＬ １０;过高的ＩＬ １０ 可能与烧伤后感染有关     

Lentiviral-mediated interleukin-4 and interleukin-13 RNA interference decrease airway inflammation and hyperresponsiveness

Interleukin (IL)-4 and IL-13 are two key cytokines released from activated T helper type 2 (Th2) cells and strongly associated with asthma and allergic disease. We applied silencing of the IL-4 and IL-13 gene expression by RNA interference delivered by a lentiviral vector to evaluate the therapeutic role of IL-4 and IL13 short hairpin RNAs (shRNAs) in a murine model of asthma. Mice were sensitized with ovalbumin (OVA), and one treatment of IL-4 and IL-13 shRNA lentiviral vector (Lenti-si-IL-4 and Lenti-si-IL-13) was instilled intratracheally 48?hr before challenge. After three challenges of OVA antigen, mice were assessed for airway inflammation and hyperresponsiveness. With infection of Lenti-si-IL-4 and Lenti-si-IL-13 in EL-4 cells, both RNA and protein expressions of IL-4 and IL-13 were obviously abrogated. Furthermore, intratracheal instillation of Lenti-si-IL-4 and Lenti-si-IL-13 in OVA-immunized mice resulted in a strong inhibition of local IL-4 and IL-13 cytokine release. Treatment with Lenti-si-IL-4 and Lenti-si-IL-13 successfully alleviated OVA-induced airway eosinophilia and Th2 cell cytokine release. Finally, to determine airway hyperresponsiveness by enhanced pause and pulmonary resistance in noninvasive and invasive body plethysmography, we found that administration of Lenti-si-IL-4 and Lenti-si-IL-13 markedly decreased airway hyperresponsiveness in OVA-immunized mice. These results suggest that inhibition of IL-4 and IL-13 gene expression by shRNA lentiviral vector markedly inhibits antigen-induced airway inflammation and hyperresponsiveness in mice.     

Colony promoting activity: differences from interleukin-3 and similarities to interleukin-6

The supernatant of long-term bone marrow culture contains colony promoting activity (CPA) which does not have granulocyte-macrophage colony stimulating activity (CSF) but which enhances granulocyte-macrophage (GM) colony formation in the presence of CSF. CPA might consist of IL-3 or IL-3-like activity, since CPA stimulates proliferation and differentiation of more immature cells to CSF-responding granulocytes-macrophage progenitors (GM-CFC), and since IL-3 also stimulates immature hemopoietic cells to proliferate and differentiate to functional blood cells. IL-1 and IL-6 are also known to enhance GM colony formation. One or both of these molecules can accordingly be another candidate for CPA. In the present study, GM-CSF activity of IL-3 was dependent on the batch of serum: it was negative in the presence of fetal calf serum, but positive in the presence of horse serum. In contrast, GM-CSF and CPA showed no such dependence on the batch of serum. The addition of IL-3 to GM colony assay system did not enhance but rather suppressed GM colony formation. The supernatant of long-term bone marrow culture which contains substantial levels of CPA did not stimulate proliferation of IL-3 dependent DA-1 cells, but facilitated the proliferation of IL-6 dependent, MH60.BSF2 cells. No detectable level of IL-1 activity was found in the supernatant. These results indicate that CPA is different from IL-1, IL-3 or GM-CSF, but similar to or the same as IL-6.     

白细胞介素-18和白细胞介素-12在儿童1型糖尿病酮症酸中毒中的作用

目的探讨白细胞介素-18(IL-18)、白细胞介素-12(IL-12)和干扰素-γ(INF-γ)在儿童1型糖尿病酮症酸中毒(DKA)中的作用。方法采用酶联免疫吸附(ELISA)方法检测61例儿童1型糖尿病(T1DM)患儿(其中28例伴DKA,33例无DKA)和30例正常对照者IL-18、IFN-γ和IL-12的血清水平。结果(1)T1DM患儿中血清IL-18水平明显比对照组高[(691．99±381．42) pg/ml vs(310．02±265．32)pg/ml,P=0．03],而两组间IFN-γ和IL-12水平则无差别。(2)DKA组患儿中IL-18和IFN-γ血清水平明显高于无DKA组[(759．25±353．82)pg/ml vs(634．93±399．79)pg/ ml,P=0．001和(9．35±8．06)pg/ml vs(5．21±6．47)pg/ml,P=0．044],而两组间IL-12血清水平则无差别。(3)IL-18和IFN-γ呈相关趋势,而与IL-12正相关。结论DKA患儿IL-18和IFN-γ血清水平明显升高,提示其可能在DKA的发生、发展中起重要作用。