白介素12与常见自身免疫性疾病的研究进展

白介素12家族的细胞因子在许多炎性和传染性疾病的宿主防御和免疫调节中都起着重要的作用。白介素12（interleukin-12,IL-12）作为其家族中一个重要的细胞因子,具有多种免疫活性,在机体早期的非特异性免疫和随后的抗原特异性免疫过程中均扮演重要角色。本文就IL-12的生物学功能、免疫调节作用以及与常见自身免疫性疾病的关系作一综述。     

白介素35在呼吸系统疾病中的作用

IL-35是新被发现的主要由Treg细胞分泌的新型抑制性细胞因子,从属于白介素12家族。其不仅可以参与T细胞的免疫应答,还可诱导产生iTr35细胞,iTr35细胞还可以进一步分泌IL-10及IL-35细胞因子,来抑制T细胞的增殖及分泌。白介素35通过抑制机体的免疫反应,阻止炎症反应损伤机体作用,IL-35表达异常且与疾病活动程度通过实验研究有明显相关,IL-35可能对呼吸系统疾病具有免疫调节和治疗的作用。但IL-35在呼吸系统疾病中的确切作用机制仍未明确,需要进一步的探讨及研究。     

IL-18与糖尿病

白介素(interleukin,IL)-18是新近发现的一种细胞因子,它能有效地诱导γ-干扰素(interferon-γ,I NF-γ)的产生,是一种多效的细胞因子,在先天及获得性免疫中均起着重要作用。它是IL-1细胞因子家族成员之一,在生物学特性上与IL-12(强Th1诱导因子)类似。IL-18是在一定免疫环境下诱导Th1或者Th2极化作用的独特细胞因子。目前已有多项研究证明IL-18与1型糖尿病的发生及2型糖尿病的发展有关,现就IL-18的最新研究进展及其与糖尿病的关系做一综述。一、IL-18的结构及生物学功能1.IL-18的结构:IL-18的三维结构最近被证实是一种类似于IL-1…     

白细胞介素27在抗病毒免疫中的作用及临床应用前景

IL-27是IL-6/IL-12家族细胞因子,可发挥广泛的免疫调节作用.IL-27可通过STAT1依赖或者非依赖途径抑制GATA-3(Th2分化的关键转录因子),从而有利于Th1的分化.IL-27引起naive T细胞产生细胞间黏附分子1,以STAT1依赖方式有利于Th1的分化.IL-27体外还可通过诱导STAT1抑制...     

IL-17细胞因子家族与炎症性肠病

Th17细胞在炎症性肠病的发病机制中起重要作用,Th17细胞主要分泌IL-17,它是一种主要由激活的CD4+T细胞表达的炎症性细胞因子,IL-17家族成员主要有IL-17A、IL-17B、IL-17C、IL-17D(IL-27)、IL-17E(IL-25)及IL-17F;IL-17细胞因子家族具有特殊的,复杂的调节性和生物功能,具有独特的免疫功能,在维持稳态和免疫疾病研究中发挥着重要的作用,同时也应正确评价针对于IL-17家族成员药物的治疗作用。     

白细胞介素33在妊娠相关疾病中的作用

白细胞介素33（IL-33）属于IL-1β家族,是新发现的核定位因子,具有抗炎、促炎双重效应。IL-33可通过参与调节母胎免疫耐受过程以维持正常妊娠,同时,IL-33在多种妊娠相关疾病中发挥重要作用,如妊娠早期IL-33的表达异常或功能障碍可导致流产;胎盘中IL-33降低致使滋养细胞功能障碍,与子痫前期患者胎盘功能不良有关;妊娠中晚期蜕膜中IL-33表达降低或功能障碍在早产的发生发展中发挥重要作用;IL-33可触发多种细胞的钙通道增加细胞内的钙离子水平,且已发现钙离子在子宫平滑肌收缩中发挥重要作用,但是关于IL-33在子宫平滑肌的研究尚待深入。而早产的发生最终都伴随着子宫平滑肌收缩, 故探讨IL-33在妊娠相关疾病以及平滑肌细胞收缩中的作用,有助于进一步研究早产的发生发展机制,从而为早产的诊治提供新思路。     

IL-23生物活性与自身免疫性疾病关系的研究

白介素(IL)-23是由p19和p40通过二硫键形成的异源二聚体分子,主要由抗原提呈细胞分泌,可促进辅助性T细胞17(Th17)的分化及产生白介素-17,是连接固有免疫和适应性免疫的重要桥梁,参与多种自身免疫性炎症性疾病的发病机制.白介素-23、白介素-23受体、白介素-23/白介素-17轴已作为临床治疗自身免疫性疾病的潜在靶向位点.白介素-23受体是造血细胞因子受体家族的成员,其单核苷酸多态性参与炎症的防御机制,是人类自身免疫重要的基因多态性位点.近年来研究显示白介素-23R基因多态性与多种自身免疫性疾病均有相关性.该文对IL-23生物学活性与自身免疫炎症性疾病的关系进行了综述.     

Th1细胞因子基因单核苷酸多态性及其交互作用在原发性肝癌中的作用

目的 探讨辅助性T细胞1(T help cell 1,Th1)细胞因子基因单核苷酸多态性(single nucleotide polymorphism,SNP)及其交互作用与原发性肝癌(简称肝癌)患病风险的关系.方法 采用病例对照研究设计方法,选择来自广西地区720例新发肝癌患者和784例非肿瘤患者为研究对象.应用TaqMan探针实时定量聚合酶链反应(polymerase chain reaction,PCR)方法对全部研究对象Th1细胞因子基因4个多态位点进行基因分型,应用Logistic 回归模型比较不同基因型与肝癌患病风险的关系,并分析单核苷酸多态性SNP-SNP交互作用在肝癌发病中的作用.结果 Th1细胞因子白介素-2(interleukin 2,IL-2)、干扰素-γ(interferonγ,IFN-γ)、白介素-1β(interleukin 1 beta,IL-1β)基因4个位点各基因型在病例组和对照组中分布差异均无统计学意义(均有P＞0.05).单个SNP位点与肝癌的患病风险无统计学关联,而携带4个Th1细胞因子危险基因型个体是携带0～1个危险基因型个体罹患肝癌风险的1.65倍.IL-2基因-330位点和IFN-γ基因-1615位点存在SNP-SNP交互作用,可增加肝癌的患病风险(OR=1.08,95％ CI:1.02～1.14).结论 单个Th1细胞因子基因SNP位点可能与广西地区人群肝癌患病风险无关联,而Th1细胞因子基因的联合作用及SNP-SNP的交互作用可增加肝癌患病风险     

白细胞介素-18与糖尿病及并发症的研究进展

白细胞介素18（IL-18）是一种细胞因子,早期称IGIF（IFN-γinducing factor）为γ-干扰素诱导因子。它是IL-1细胞因子家族成员之一,在生物学特性上与IL-12（强Th1诱导因子）类似。IL-18是在一定免疫环境下诱导Th1或者Th2极化作用的独特细胞因子。来源于单核细胞及巨噬细胞,具有刺激T细胞增殖,增强细胞及NK细胞活性,并具有抗肿瘤、抗感染、免疫调节等多种生物学作用。可与许多细胞因子相互作用,参与了自身免疫性疾病和变态反应性疾病的发生,在许多疾病的基础性研究和临床应用中有重要前景。目前已有多项研究证明IL-18与1型糖尿病的发生及2型糖尿病的发展有关,并与糖尿病并发症密切相关。现就IL-18的发现、来源、分布、结构特点、生物学作用以及与糖尿病及并发症方面的研究进展做一综述。     

白细胞介素-18与成人Still's病

<正> 白介素-18(IL-18)是一种新发现的细胞因子,早在1989年Nakamura就在LPS(脂多糖)诱导的鼠脾细胞血清中发现了一种共刺激因子,可与IL-12或分裂原协同诱导IFN-γ的产生,1996年由Ushio正式命名为IL-18,根据它的分子结构、氨基酸序列,受体、信号传导途径和其在炎症前的介导作用,证明IL-18属于IL-1家族。IL-     

Cytokine production patterns and antibody response to measles vaccine

Cytokines play an important role in the immune response to live measles virus immunization. To gain further insight into the cytokine production profile in response to measles vaccination, we studied interferon-gamma (IFN-gamma), tumor necrosis factor (TNF-alpha), soluble IL-2 receptor (sIL-2R), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-6 (IL-6) in both supernatants from peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA), and plasma. We enrolled 57 healthy infants and children residing in an area where no measles virus circulated in their lifetimes. Overall analysis of cytokines in supernatants from PBMC showed that a predominant Th1 cytokine pattern occurs after the second dose of measles immunization. However, plasma levels of Th1 cytokines (IFN-gamma, sIL-2R and TNF-alpha) were preferentially activated by measles virus after the first dose of measles vaccination. Median IFN-gamma plasma levels were 1.73 pg/ml for infants compared to 0.63 pg/ml for older children (P = 0.003). These data suggest that after the first and the second dose of measles virus immunization, there is a predominant Th1-type directed immune response, but the Th1 cytokine pattern seems to be stronger in previously unvaccinated children. There was no correlation between cytokine production by PBMC supernatants after PHA stimulation and circulating levels of plasma cytokines. No relationship was found between any specific cytokine level and measles antibody level.     

Obesity, inflammation and insulin resistance: role of gp 130 receptor ligands

Obesity can be considered as a low grade inflammatory disease, characterized by increased plasma levels of proinflammatory cytokines such as tumoral necrosis factor-a (TNF-a), and acute phase reactant proteins like C-reactive protein. In this context, some cytokines of the interleukin-6 (IL-6) family have been involved in the inflammatory processes associated to obesity. In addition to IL-6, the IL-6 cytokine family includes IL-11, ciliary neurotrophic factor (cntf), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF) y Oncostatin M (OsM). These proteins are also known as gp130 cytokines because all of them exert their action via the glycoprotein 130 (gp130) as a common transducer protein within their functional receptor complexes. However, their role in obesity and related disorders is controversial; thus, whereas some studies have described the involvement of gp130 cytokines in the development of obesity and its related cluster of pathophysiologic conditions like insulin-resistance, fatty liver and cardiovascular diseases, other trials have proposed the gp130 receptor ligands as therapeutic targets in the treatment of obesity and its related disorders. In fact, CNTF treatment has demonstrated to be effective in the reduction of body weight, by promoting the inhibition of food intake and the activation of the energy expenditure, together with an improvement of insulin sensitivity. This review analyzes the potential therapeutic role of some of the gp130 ligands in obesity and related diseases.     

Nutritional aspects of leukocytic cytokines

Immune responses result in a variety of metabolic adjustments that are mediated by cytokines of leukocytic origin. Of the dozens of cytokines released during an immune response, interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are the major mediators of intermediary metabolism. These three cytokines act in concert to decrease food intake, increase resting energy expenditure, gluconeogenesis, glucose oxidation, and hepatic synthesis of fatty acids and acute phase proteins, decrease fatty acid uptake by adipocytes and alter the distribution of zinc, iron and copper. Most of these activities result from direct interactions between the cytokine and the responding cells. IL-1, TNF alpha and IL-6 also affect changes in metabolism by changing levels of circulating insulin, glucagon and corticosterone. The nutritional impact of these metabolic changes is dependent upon age. In growing animals, increases in energy expenditure and oxidation of amino acids are balanced by lower needs associated with growth. In adult animals, energy and amino acid requirements are increased by an amount similar to the increased basal metabolic rate and amino acid oxidation. Nutrition also influences the release of cytokines and consequently affects regulation of the immune response. For example, protein deficiency results in decreased IL-1 release and impaired tissue responses to IL-1.     

Behavior-immunity relationship: the role of cytokines

There are several phenomena in which the immune and the central nervous systems regulate each other. However, their mechanisms are poorly understood. Since cytokines have a central role in the regulation of the immune response, this review describes their participation in two forms of neuro-immune communication, immunomodulation by psychological stress and behavioral conditioning of immune response. The role of cytokines in the endocrine and behavioral effects of acute phase, where cytokines have an effect in functions of the central nervous system, is also reviewed. The effects of psychological stress are described as both immunosuppressing and immunoenhancing. Among them, a relevant immunosuppressing one is the reduction of IL-1, IL-2, and IFN-gamma levels. In contrast, some of the pro-inflammatory effects of stress are mediated by an increase in the levels of IL-6, IL-1, and TNF mediated by the neurotransmitter Substance P. A possible role for IL-1 and IFN-beta as possible messengers in immune regulation by behavioral conditioning is proposed. Pro-inflammatory cytokines in turn can activate the hypothalamus-pituitary-adrenal axis and induce sickness behavior during the acute phase response, during which the parasympathetic nervous system serves as pathway for their detection by the central nervous system. An account is given about recent findings on the regulation of cytokine expression by neurotransmitters from the sympathetic nervous system (epinephrine and norepinephrine), a key piece in all these mechanisms of brain-immune communication. Possible mechanisms and pathways of communication between the brain and the immune system, as well as the possible participation of other cytokines are discussed.     

IL-6家族细胞因子在肺纤维化中的作用

肺纤维化是以成纤维细胞增殖、大量细胞外基质聚集,以及伴随炎症损伤、组织结构破坏为特征的一大类肺疾病的终末期改变;炎症反应在纤维化发病过程中尤其起到关键作用。白细胞介素-6( interleukin-6, IL-6)家族细胞因子作为促炎细胞因子或抗炎细胞因子参与肺部炎症反应,通过调控促纤维化因子分泌,激活信号传导通路,诱导成纤维细胞的增殖、分化,从而在肺纤维化进展中发挥重要作用。本文拟对IL-6家族细胞因子在肺纤维化中的作用与治疗研究进行综述,以供今后工作参考。     

Contribution of interleukin 2 and interleukin 12 receptors in signal transduction during cell activation of the immune system

Interleukin-2 (IL-2) and interleukin-12 (IL-12) belong to lympho-hematopoietic cytokines and play a critical role in the promotion and enhancement of cellular response. IL-2 as the second signal of antigenic stimulation facilitates the transition of the cell cycle from phase G1 to phase S and is responsible for the regulation of T lymphocytes proliferation and the activation of cytotoxic T cells, natural killers, macrophages and granulocytes. IL-12 is the dominant factor in T helper cells polarization leading to the secretion of IFN-gamma. Receptors for both of the cytokines (IL-2R or IL-12R) represent class I cytokine receptors composed of multiple subunits. Generally, they contain a similar extracellular conserved motif of four cysteines, and amino acid sequence--WSXWS (interacting directly with ligand) but possess no catalytic domens in the intrinsic tail of the chains. For this reason, to transfer the impact, the association with number of signaling molecules, allowing the activation of the signaling pathways is required. The connections of IL-2R or IL-12R with their ligands recruit receptor-associated cytoplasmic proteins from the JAK family (JAK1/JAK3 or JAK2/TYK2, respectively), which catalyze the phosphorylation of themselves and intrinsic tyrosine residues on the receptor, creating STAT docking sites. This phosphorylated and subsequent dimerised proteins bind rapidly to DNA and activate it. This review, presents the differences and similarities between the signaling pathways triggered by IL-2R or IL-12R ligation.     

Die Rolle von Zytokinen in der Pathogenese und Therapie chronisch-entzündlicher Darmerkrankungen

Crohn's disease and ulcerative colitis are chronic disorders of the gastrointestinal tract. Crohn`s disease is characterised by a transmural inflammation that can affect any part of the human gastrointestinal tract, whereas ulcerative colitis is restricted to the colon.Both diseases are disorders mediated by a pathogenic proinflammatory cytokine pattern produced by T-cells and macrophages. Inflammatory bowel diseases arise in individuals who are genetically susceptible as a result of a pathological immune response to mucosal bacterial antigens. In Crohn's disease, the interaction of macrophages and T-cells induces the production of proinflammatory cytokines, such as TNF-α, IL-12, IL-6 and IFN-γ. In the last decade these molecular mediators, their receptors and their mechanisms of action were characterised.Since then treatment has changed and new approaches based on the knowledge about cytokine interactions has been developed.One possibility to inhibit a proinflammatory cytokine response is to inhibit cell-cell interactions by blocking adhesion molecules (α4β1, α4β7) or costimulatory molecules (CD40L). The pathologic cytokine action in the inflamed gut can be counteracted in different ways. On the one hand clinical trials showed, that the function of proinflammatory cytokines can be neutralized by cytokine-antibodies (TNF-α, IL-12),by cytokine receptorantibodies (TNF-α, IL-6R) or by inhibiting the synthesis of proinflammatory cytokines by the application of antisense-oligonucleotides (TNF-α converting enzyme).On the other hand the application of protective antiinflammatory recombinant cytokines (IL-10, IL-11 and IFN-α) might protect individuals from an overwhelming proinflammatory immune response.The most effective cytokine antibody in the treatment of Crohn's disease so far is the anti-TNF-antibody infliximab,which may also cause serious side effects (e.g. tuberculosis reactivation).     

血吸虫肝纤维化的病理机制

血吸虫肝纤维化主要由宿主对虫卵及其引起的肉芽肿产生免疫应答所致,整个过程主要有中性粒细胞、嗜酸性粒细胞、B细胞、T细胞、肝星形细胞(HSC)等多种细胞参与,并受到TNF-α、IL-1、IL-6、IFN γ等Th1型和IL-4、IL-5、IL-10、IL-13等Th2型细胞因子及一些趋化因子的调控.其反应过程十分复杂,目...