IL-25在支气管哮喘中的作用

白介素25(Interleukin-25,IL-25)是细胞因子IL-17家族的成员之一,主要由活化的Th细胞和肥大细胞所分泌。IL-25能够诱导释放Th2型细胞因子IL-4、IL-5、IL-13,炎性细胞因子IL-6,Th1型趋化因子CXCL10、CXCL9、CCL5的产生,导致嗜酸性粒细胞的浸润,在支气管哮喘的发病中起重要作用,本文就此作一综述。     

血清IL-17 与IL-23 在支气管哮喘患者中的表达水平及其相关性

目的:探讨IL-17与IL-23在支气管哮喘患者血清中的表达水平及其相关性。方法:选择2010年2月~2015年9月在我院进行诊治的支气管哮喘患者98例,其中包括56例为缓解期组,42例为急性发作期组,对照组为20例体检健康者,观察三组的血清IL-17、IL-23水平及肺功能指标的差异,并分析其相关性。结果:与对照组相比,缓解期组和急性发作期组血清IL-17、IL-23水平均明显升高(P0.05),急性发作期组血清IL-17、IL-23水平均显著高于缓解期组(P0.05);急性发作期组患者的PEF%、FEV1%、V50%、V25%均明显低于缓解期组,差异有统计学意义(P0.05);哮喘患者血清IL-17水平与IL-23水平呈正相关(r=0.685,P=0.000),血清IL-17与FEV1负相关(r=-0.592,P=0.000)、与PEF负相关(r=-0.515,P=0.000),IL-23与FEV1负相关(r=-0.598,P=0.000),与PEF负相关(r=-0.532,P=0.000)。结论:血清IL-17和IL-23的高表达可能参与了支气管哮喘的形成,并能影响疾病的进程,两者表达水平密切相关。     

Th22细胞与支气管哮喘

支气管哮喘是一种临床上常见的呼吸道疾病,研究发现CD4＋T细胞在哮喘的发病过程中起重要作用。Th22细胞是最近发现的一类CD4＋T细胞功能亚群之一,其主要效应因子IL-22在炎症性疾病、组织修复、创口愈合及自身免疫性疾病中起重要作用,但其具体机制尚未完全清楚。从Th22的细胞因子来源、生物学特性、分化和调控出发,简要探讨Th22细胞与哮喘之间的可能关系。     

支气管哮喘患者血清IL-4、TNF-α 及IgE 水平变化及临床意义

目的:研究支气管哮喘患者白细胞介素-4(IL-4)、肿瘤坏死因子-α(TNF-α)及免疫球蛋白E(IgE)水平变化及临床意义.方法:对78例支气管哮喘患者(急性发作期组39例、缓解期组39例)血清IL-4、TNF-α、IgE水平进行检测,并与正常对照组的40例健康受试者进行比较分析.结果:支气管哮喘患者组血清IL-4、TNF-α、IgE水平显著高于正常对照组,差异均有统计学意义(P＜0.05);急性发作期组血清IL-4、TNF-α、IgE水平均显著高于缓解期组,差异亦均有统计学意义(P＜0.05);支气管哮喘患者血清IL-4、TNF-α、IgE水平两两之间呈正性显著相关(P＜0.05).结论:检测支气管哮喘患者血清IL-4、TNF-α、IgE水平对患者疾病预测及治疗具有重要的临床意义.     

高体重指数支气管哮喘患者血清中IL-8、IL-10及INF-γ的研究及意义

目的:探讨高体重指数支气管哮喘患者血清中IL-8、IL-10及INF-γ的变化及临床意义。方法:选择高体重指数支气管哮喘患者(36例)、正常体重指数支气管哮喘患者(32例)以及健康人(32例),采用双抗体夹心ELISA法检测其急性发作期和缓解期血清中IL-8、IL-10和INF-γ的水平。结果:①高体重指数支气管哮喘组与正常体重指数支气管哮喘组急性发作期血清中IL-8水平显著高于缓解期以及对照组的水平(P<0.05)。②在缓解期,高体重指数支气管哮喘组血清中IL-8水平仍高于正常体重指数支气管哮喘组和对照组的水平(P<0.05)。③在急性发作期,高体重指数支气管哮喘组和正常体重指数支气管哮喘组血清中IL-10水平均显著低于其在缓解期及对照组的水平(P<0.05)。④三组间血清INF-γ水平在急性期与缓解期均无明显差异(P>0.05)。结论:血清中IL-8是高体重指数支气管哮喘患者发病过程中的重要炎症因子,并且始终参与其中。IL-10可能是支气管哮喘的抑炎因子,其缺乏可能是导致哮喘患者急性发作的因素之一。     

氧化苦参碱对哮喘大鼠肺组织IL-10 表达的影响

目的:观察不同浓度氧化苦参碱(Oxymatrinem,Oxy)对哮喘大鼠肺组织IL~(-1)0表达的影响,并探讨其作用机制。方法:构建哮喘大鼠模型,将40只清洁级健康雌性SD大鼠随机分成5组,每组8只:A:哮喘组(仅卵蛋白(Ovalbumin,OVA)致敏)、B:低浓度组(Oxy 50 mg/kg)、C:中浓度组(Oxy 100 mg/kg)、D:高浓度组(Oxy 150 mg/kg)、E:对照组(生理盐水),末次激发24 h后处死全部大鼠,取大鼠肺脏,HE染色观察肺组织病理改变,采用RT-PCR、Western Blot测定各组肺组织中IL~(-1)0基因及蛋白水平的表达。结果:HE结果显示,哮喘组可见大量炎症细胞浸润,气管平滑肌明显增厚。对照组肺泡壁薄且光滑,未见明显炎性细胞的浸润,不同浓度氧化苦参碱药物干预组其肺组织炎症细胞浸润及气管平滑肌病变程度随着用药浓度的增高呈逐渐减轻趋势。RT-PCR以及Western blot检测IL~(-1)0发现,哮喘组、氧化苦参碱低浓度组、氧化苦参碱中浓度组与对照组相比IL~(-1)0的表达均有所减低(P0.05),而氧化苦参碱高浓度组与对照组比较,IL~(-1)0的表达无统计学意义(P0.05);氧化苦参碱中浓度组、氧化苦参碱高浓度组与哮喘组相比IL~(-1)0的表达均有所增高(P0.05),氧化苦参碱低浓度组与哮喘组相比IL~(-1)0的表达无统计学意义(P0.05)。结论:氧化苦参碱抑制、控制哮喘发作可能与促进肺组织中IL~(-1)0基因、蛋白的表达相关,且促进程度在一定范围内与浓度呈正比。     

Th2型细胞因子在支气管哮喘发作过程中的表达

支气管哮喘是由多种细胞特别是肥大细胞、嗜酸性粒细胞和T淋巴细胞参与的慢性气道炎症。对支气管哮喘发病机制的认识近年有重大改变 ,Th2型细胞的作用被认为是支气管哮喘发作过程的中心 ,综述了由Th2型细胞产生的细胞因子在支气管哮喘发病过程中的作用及意义。     

诱发支气管哮喘动物模型气道重塑特征的方法和评价

气道重塑是慢性哮喘最复杂的病理基础之一,建立具有气道重塑特征的支气管哮喘动物模型对评价药效及阐明病理机制的研究具有重要的意义.通过对相关动物模型进行分析比较,总结可行的支气管哮喘气道重塑动物模型构建方法.     

易感基因多态性与支气管哮喘的相关性研究

目的:探讨白介素-4(Interleukin-4,IL-4)基因589位点、白介素-4受体(interleukin-4 receptor,IL-4R)基因576位点多态性与内蒙古地区汉族支气管哮喘患者是否存在遗传易感性,是否与血清总IgE浓度相关.方法:采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测内蒙古地区62例支气管哮喘患者和30例汉族正常人群IL-4基因的589位点、IL-4R基因的576位点多态性,进行基因型和基因频率分析,同时采用Elisa法检测患者血清总IgE浓度.结果:哮喘组IL-4基因启动子区-589(C/T)位点多态性分布频率与对照组比较,两组间基因型频率分析(X2=3.437,P=0.179),无显著性统计学差异(P＞0.05);两组基因频率分析(X2=9.405,P=0.002),有显著性差异(P＜0.05).哮喘组IL-4R基因启动子区-576(Q/R)位点多态性分布频率与对照组比较,两组间基因型频率分析(X2=0.815,P=0.665),无显著性统计学差异(P＞0.05),两组基因频率分析(X2=0.245,P=0.621),无显著性差异(P＞0.05).哮喘组血清总IgE浓度高于对照组,有显著性差异(t=6.367,P=0.00,P＜0.05).结论:内蒙古地区汉族人群哮喘组中,IL-4基因启动子区-589(C/T)位点多态性与支气管哮喘的发病无显著性差异;IL-4R基因-576(Q/R)位点多态性与支气管哮喘的发病无显著性差异;患者组血清总IgE显著高于对照组,但是与IL-4基因启动子区-589(C/T)位点多态性和IL-4R基因-576(Q/R)位点多态性没有相关性.     

IL-13在支气管哮喘中的作用机制及治疗靶位

支气管哮喘是由多种细胞包括气道炎性细胞、结构细胞和多种细胞组分参与的气道慢性炎症性疾病。其发病原因复杂,以反复发作的呼吸困难、气道的高反应性和慢性炎症为特点。细胞因子作为免疫活性细胞中的效应分子,具有的免疫调节作用,诸多学者认为白介素-13(interleukin-13,IL-13)在哮喘发病中扮演重要角色,其拮抗剂有望成为哮喘治疗的新方法,本文欲将IL-13的生物学功能、IL-13在支气管哮喘中的作用机制及干预治疗靶位加以综述,为制定哮喘防治策略、开发新治疗技术提供新思路。     

Effects of catalpol on bronchial asthma and its relationship with cytokines

An animal (BALB/c mice) model of catalpol associated with bronchial asthma in vivo was established, and the effects of catalpol and its relationship with cytokines were investigated. A total of 30 adult BALB/c mice were randomly divided into a positive control group, a model group, and a catalpol group, with 10 mice in each group. The lung function of mice, the cell count, and the cytokine concentrations in bronchoalveolar lavage fluid (BALF) were detected. The levels of cytokines [interleukin 4 (IL-4), interleukin 5 (IL5), and interferon gamma (IFN-γ)] in BALF were measured with enzyme-linked immunosorbent assay methods. The total number of cells in the BALF of the group treated with catalpol was significantly lower than the model group. After treatment with catalpol, the eosinophils and neutrophils of the mice were remarkably reduced compared with the model group. The malondialdehyde content in the lung tissue homogenate of the mice was also decreased in the catalpol group. The cytokines IL-5 and IL-4 exhibited a similar tendency: the concentrations of IL-4 and IL-5 for the catalpol group were dramatically decreased compared with the model group. However, the IFN-γ concentration for the catalpol group was higher than the model group. The results indicated that IL-5 may involve in the pathologic process of asthma-like IL-4, and an inflammatory reaction may still exist in the airway during the remission stage of asthma. The imbalances of the cytokine network might be an important molecular basis in the asthma pathogenesis. It is suggested that catalpol may be a potential drug for the clinical treatment of asthma.     

Uptake of 12-HETE by human bronchial epithelial cells (HBEC): Effects on HBEC cytokine production

12-HETE, the major lipoxygenase end-product of platelets and macrophages, may be released in contact of bronchial epithelium in inflammatory diseases of the lung. We have studied the outcome of 12-HETE in presence of human bronchial epithelial cells (HBEC). When HBEC were incubated with [³H]12-HETE for 30 minutes, 27.5% of total radioactivity was found in HBEC and 72.5% in supernatants. Unesterified 12-HETE accounted for 22.4% of total radioactivity, 4.5% being recovered in phospholipids, preferentially in phosphatidylcholine and phosphatidylethanolamine. No incorporation in neutral lipids was detected. 72.9% of the incubated radioactivity was recovered in un identified metabolites. As 12-HETE has been shown to modulate the expression and production of various proteins, the consequence of the 12-HETE uptake on the release of GM-CSF and IL8 by HBEC was assessed. HBEC from control subjects were cultured for 24 hours with 12-HETE (10⁻⁹ to 10⁻⁷M) in the presence or absence of TNFα. Detectable amounts of both cytokines were released in the supernatant in basal conditions at 24hr, and TNFα increased significantly the release of GM-CSF. 12-HETE at 10⁻⁷M weakly but significantly decreased the TNF-induced release of GM-CSF from HBEC. Thus the uptake of 12-HETE could affect the epithelial cell function in some situations.     

Seasonal allergic asthma and non-specific bronchial responsiveness

Summary Bronchial responsiveness to methacoline (PD20 FEV1 mcg) was measured in 64 non smoker asthmatic patients with baseline FEV190% predicted. Patients underwent skin prick tests (SPT) and RAST.Allergic patients had: SPT3+ and RAST-score>II class to the same antigen and correlation with asthmatic symptoms; non allergic patients had negative SPT and RAST. We divided patients in four groups: 1st) allergic seasonal asthmatics before pollen season; 2nd) allergic seasonal asthmatics during pollen season; 3rd) allergic perennial asthmatics; 4th) non-allergic perennial asthmatics.A significant difference in log PD20 was observed between 1st and 2nd group (p<0.0005); between 1st and 3rd group (p<0.0005); between 1st and 4th group (p<0.0005). In allergic seasonal asthmatics before pollen season 10/20 subjects were non-responsive to methacholine (PD201600 mcg), while in 2nd, 3rd and 4th group no subjects were non-responsive.The authors conclude that non-specific bronchial hyperresponsiveness to methacoline is not constant in seasonal allergic asthmatics out of pollen season.     

IL-4 和IL-12 在宫颈癌中的表达及对紫杉醇过敏的影响

目的:研究IL-4,IL-12在宫颈癌组织中的表达,探讨其对宫颈癌发生及术后对紫杉醇过敏的影响。方法:应用半定量逆反应-聚合酶链反应(RT-PCR)技术检测IL-4mRNA,IL-12p35以及IL-12p40 mRNA在正常宫颈组和宫颈癌组中的表达,并分析两者之间的相关性以对紫杉醇过敏的影响。结果:1.宫颈癌组中IL-4mRNA表达水平高于正常宫颈组,而IL-12p35和IL-12p40mRNA表达低于正常宫颈组,差异有统计学意义(P<0.05);2.在术后给予紫杉醇治疗的宫颈癌患者中,过敏组中IL-4mRNA的表达高于不过敏组;IL-12p35和IL-12p40mRNA则低于后者,差异有统计学意义(P<0.05)。结论:体内IL-12降低和(或)IL-4升高可促进宫颈癌的发生发展增加紫杉醇过敏的发生率。     

双歧杆菌对过敏性哮喘儿童树突状细胞分泌IL-10、IL-12等细胞因子的影响

目的探讨双歧杆菌对过敏性哮喘儿童外周血单核细胞（PBMC）来源的树突状细胞（DC）分泌IL-1β、IL-6、IL-10、IL-12、IL-23和IFN-γ的影响。方法从15例过敏性哮喘儿童和15例非哮喘儿童的外周血单个核细胞诱导生成未成熟DC,加入双歧杆菌后继续培养DC2d,用ELISA方法检测培养上清中IL-1β、IL-6、IL-10、IL-12、IL-23和IFN-γ的水平。结果双歧杆菌能明显刺激哮喘儿童DC分泌IL-12、IFN-γ,IL-1β及IL-6和非哮喘儿童DC分泌IL-12、IL-10、IL-1β及IL-23水平增高。结论双歧杆菌能够刺激过敏性哮喘儿童DC分泌IL-12和IFN-γ,可能改变Th2优势分化,纠正Th1／Th2失衡。同时双歧杆菌还能刺激哮喘儿童DC分泌IL-1p及IL-6增高,达到促进,Th17细胞分化的作用。     

Difference in response of NK cell activity in newborns and adult to IL-2, IL-12 and IL-15

The killing activity of cord blood mononuclear cells (cMNC) against cytomegalovirus (CMV)-uninfected and -infected fibroblasts was comparable to that of adult peripheral blood mononuclear cells (aPBMC). The killing activity of cMNC against K562 cells was significantly lower compared with that of aPBMC. Treatment of cMNC and aPBMC with interleukin-2 (IL-2), IL-12 or IL-15 significantly enhanced killing activity against K562 cells and CMV-uninfected and -infected cells. By comparison of cMNC with aPBMC, killing activity against the K562 cells of cMNC was augmented to the level of aPBMC when cultured with IL-2, IL-12 or IL-15. The killing activity of cMNC against CMV-uninfected and -infected fibroblasts did not increase to the level of adult PBMC by treatment with IL-2, IL-12 or IL-15. These data suggest that cord blood contains a functionally different NK cell subpopulation than that among adult NK cells.     

Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275

Cytokines interleukin (IL)-12 and IL-23 are implicated in the pathogenesis of psoriasis. IL-12 causes differentiation of CD4+ T cells to interferon-gamma (IFN-gamma)-producing T helper 1 (Th1) cells, while IL-23 induces differentiation to IL-17-producing pathogenic Th17 cells. The effects of the monoclonal antibody to IL-12/23 p40 subunit (CNTO 1275) on IL-12 receptor (IL-12R) expression, markers associated with skin homing, activation, and cytokine secretion were investigated in vitro using human peripheral blood mononuclear cells (PBMCs) from healthy donors. PBMCs were activated in the presence or absence of recombinant human (rh) IL-12 or rhIL-23, with or without CNTO 1275. CNTO 1275 inhibited upregulation of CLA, IL-12R, IL-2Ralpha and CD40L expression and also inhibited IL-12- and IL-23-induced IFN-gamma, IL-17A, tumor necrosis factor (TNF)-alpha, IL-2, and IL-10 secretion. Thus, the therapeutic effect of CNTO 1275 may be attributed to the IL-12/23 neutralization, resulting in decreased expression of skin homing and activation markers, and IL-12- and IL-23-induced cytokine secretion.     

IL-12-and IL-23 in health and disease

Interleukin (IL)-12 and IL-23 play important roles in the development of experimental autoimmune disease models and numerous afflictions affecting humans. Preclinical data over the last 20 years combined with successful clinical trials has identified a clear relationship between IL-12, IL-23 and the generation of pathogenic T helper cells capable of orchestrating tissue inflammation. Observations made in the clinic have shown that IL-12p40, a common subunit shared by IL-12 and IL-23, is critical to pathologies associated with psoriasis, inflammatory bowel disease (IBD) and tumor growth. These advancements have set in motion the development of a number of potential therapeutics aimed at manipulating IL-12/23 signaling pathways in both mice and humans. This review will discuss a brief history of the understanding and expansion of the IL-12 cytokine family, some difficulties associated with preclinical data interpretation and finally the medicinal interventions that have been developed to combat IL-12/23-driven autoimmune disorders.