吸入糖皮质激素对哮喘患者Th1/Th2细胞因子网络影响

支气管哮喘(哮喘)是一种慢性气道炎症疾病,多种炎性细胞和炎性介质参与其过程。目前认为T辅助淋巴细胞两个功能性亚群Th1／Th2相关细胞因子在哮喘发病中发挥重要作用。我们对哮喘患者白细胞介素-5(IL-5)、白细胞介素-8(IL-8)r-干扰素(IFN-r)水平进行检测,探讨吸入糖皮质激素对哮喘患者Th1／Th2细胞因子的影响。     

Th17细胞与肝脏疾病

辅助性T细胞(Th细胞)根据产生细胞因子和生物学功能分为Th1和Th2细胞.最近研究发现了一种与Th1和Th2细胞亚群不同的活化CD4+T细胞亚群-Th17细胞.TGF-β与IL-6或IL-21的协同作用,诱导Th17细胞分化.IL-12家族的IL-23在促进IL-17分泌、增强Th17细胞效应功能方面发挥重要作用,而RORγt是其特异性转录因子.分化成熟的Th17细胞可以分泌IL-17A、IL-17F、IL-21、IL-22、IL-6、TNF-α等多种细胞因子,在介导炎性反应(防御病原菌感染)、自身免疫性疾病、肿瘤、移植排斥反应等过程中发挥重要作用.Th17细胞也为研究肝脏疾病的发病机制及防治策略提供了新思路和方向.     

白介素18与代谢综合征的关系研究进展

白介素18可诱导γ—干扰素的产生，加强1型辅助性T淋巴细胞(Th1)的反应，参与了很多疾病的病理过程，且IL-18和脂肪细胞因子之间有着复杂的相互作用。研究发现2型糖尿病患者血浆中IL-18水平升高，且IL-18的水平与血糖、血脂水平及内脏脂肪含量呈正相关。IL-18还可能参与了动脉粥样硬化斑块的形成。内源性IL-18抑制剂——IL-18结合蛋白可阻断IL-18的作用。     

肝炎患者血清IL-12、IFN-γ和IL-10检测的意义

目的:探讨检测IL-12、IFN-γ和IL-10对病毒性肝炎患者的临床意义。方法:利用ELISA法检测97例病毒性肝炎患者血清IL-12、IFN-γ和IL-10水平,动态观察45例接受免疫增强剂治疗的慢性肝炎患者上述细胞因子的变化。结果:急性肝炎患者血清IL-12及IFN-γ水平均明显升高(P<0.01);慢性肝炎、肝硬化患者血清中IL-10明显高于正常对照组(P<0.01)。免疫增强剂治疗获得完全应答反应的患者治疗期间血清IL-12、IFN-γ水平明显上升(P<0.01),IL-10水平下降(P<0.05),无应答者治疗过程中上述细胞因子无明显变化。结论:Thl型免疫应答对机体清除病毒起关键作用;Th2型免疫应答与感染慢性化及疾病持续发展有关;免疫治疗可使部分Th2型免疫应答占优势的慢性肝炎患者转化为Th1型占优势。     

Th17细胞与肝脏疾病

辅助性T细胞（Th细胞）根据产生细胞因子和生物学功能分为Th1和Th2细胞。最近研究发现了一种与Th1和Th2细胞亚群不同的活化CD4^＋T细胞亚群-Th17细胞。TGF-8与IL-6或IL-21的协同作用,诱导Th17细胞分化。IL-12家族的IL-23在促进IL-17分泌、增强Th17细胞效应功能方面发挥重要作用,而RORγt是其特异性转录因子。分化成熟的Th17细胞可以分泌IL-17A、IL-17F、IL-21、IL-22、IL-6、TNF—α等多种细胞因子,在介导炎性反应（防御病原菌感染）、自身免疫性疾病、肿瘤、移植排斥反应等过程中发挥重要作用。Th17细胞也为研究肝脏疾病的发病机制及防治策略提供了新思路和方向。     

白介素17在结核病发生和发展中的免疫应答作用

分泌白介素17(IL-17)的辅助型T细胞17(Th17)参与结核病的免疫应答,并与Th1共同参与对结核病的免疫调控.IL-17对机体防御结核分枝杆菌感染具有保护性作用,它通过促进中性粒细胞的生成和募集,加强干扰素γ的保护性反应,促进肉芽肿的形成而达到控制结核分枝杆菌的作用.但是.IL-17过度表达则会引起机体的损伤,...     

椎间盘突出患者骨髓血血清Th1、Th2、IL-12及IL-4的表达及临床意义

目的探讨Ⅰ型辅助性T细胞(Th1)、Ⅱ型辅助性T细胞(Th2)、白细胞介素(IL)-4和IL-12在椎间盘突出(LDH)患者骨髓血血清中的表达水平及其临床意义。方法选取该院2013年9月至2015年9月住院的腰椎骨折并摘除椎间盘的患者15例(对照组)及手术治疗LDH患者15例(观察组),分别抽取两组骨髓血,分离骨髓血血清,流式细胞术用以检测骨髓血血清中Th1和Th2细胞数,酶联免疫吸附法(ELISA)用以检测IL-4和IL-12的表达。结果观察组骨髓血血清中Th1和Th2的细胞数高于对照组(P<0.05),观察组骨髓血血清中IL-12的表达高于对照组(P<0.05),而两组IL-4的表达差异无统计学意义(P>0.05),观察组骨髓血血清中IL-12与IL-4的表达呈负相关(r=-0.320,P<0.05)。结论 LDH患者血清中Th1和Th2细胞数增加,Th1分泌的细胞因子IL-12的表达增加,Th1及其分泌的细胞因子IL-12可能参与LDH疾病的发生发展。     

白细胞介素-27的生物学功能与应用前景

白细胞介素(IL)-27是一种新发现的IL-12家族细胞因子,主要由激活的抗原提呈细胞产生。IL-27促进初始CD4 T细胞增殖,使其向Th1细胞方向分化,同时抑制Th2和Th17分化,并协同IL-12刺激细胞产生干扰素(IFN)-γ。在Th1高度活化时,IL-27却可以限制Th1型应答的强度。由于IL-27具有促进Th1型反应和减轻炎症的双重作用,它可能是多种以Th1型反应为主的病理过程(如感染免疫,自身免疫病和抗肿瘤免疫)的关键性调节因子。应用或拮抗IL-27可能对感染和自身免疫病有益,IL-27也有望成为治疗肿瘤的靶基因。     

老年急性冠状动脉综合征患者辅助性T淋巴细胞的研究

目的 通过分析老年急性冠状动脉综合征(ACS)患者外周血中辅助性T淋巴细胞亚群1(Th1)和亚群2(Th2)频率的变化,探讨辅助性T淋巴细胞在ACS进程中的作用.方法 通过细胞内细胞染色对32例ACS患者(ACS组)、35例稳定性心绞痛(SAP)患者(SAP组)及20例健康体检者(对照组)的外周血单个核细胞进行Th1、Th2分型,ELISA法检测血浆Th1、Th2相关细胞因子水平:干扰素-γ(IFN-γ)、白细胞介素2(IL-2)、白细胞介素4(IL-4)和白细胞介素10(IL-10).结果 ACS组患者Th1细胞较SAP组及对照组明显升高(P＜0.05);3组间Th2细胞变化无统计学差异(P＞0.05).ACS组患者Th1相关细胞因子IFN-γ和IL-2较SAP组和对照组明显升高(P＜0.05);ACS组患者Th2相关细胞因子IL-10较SAP组和对照组明显降低(P＜0.05),IL-4低于检测水平;IFN-γ和IL-2水平与Th1的升高密切相关(P＜0.05).结论 Th1和Th2的失衡与ACS的发生密切相关,其相关细胞因子IFN-γ和IL-2水平的升高,使系统炎性反应进一步恶化.     

Th17细胞与肝脏及相关疾病的研究进展

人体免疫类型包括特异性（获得性）免疫和非特异性（固有）免疫,其中特异性免疫主要由T淋巴细胞和B淋巴细胞参与。辅助性T细胞（Th细胞）由CD4＋T细胞分化成熟而来,在机体细胞免疫及体液免疫中发挥重要作用。1986年Mosmann等,将Th细胞根据其分泌的细胞因子以及在机体免疫中的不同作用,把Th细胞分为Th1和Th2细胞亚群［1］。在IFN-γ及IL-12的协同作用下,CD4＋T细胞分化成熟为Th1细胞,并分泌肿瘤坏死因子α（TNF-α）、γ干扰素（IFN-γ）、白介素（IL-2）等,在抗细胞内感染和细胞免疫反应中起到重要的作用。     

白介素23及其受体的致炎机能

白介素23(IL-23)是一个由IL-23p19和IL-12p40组成的异二聚体细胞因子,属IL-12炎症因子家族成员.它广泛参与体内免疫过程,调节免疫细胞的分化发育、增殖及炎症反应.IL-23受体复合物由IL-12R131和IL-23R两个亚基构成.IL-23受体的致病作用与通过IL-23-信号转导和转录激活因子3-Thl7-IL-17途径介导免疫异常有关.在治疗慢性炎症方面,以IL-23配体或受体为靶点的单克隆抗体已取得初步成效.对IL-23/IL-23受体基因及其致病途径的深入研究,将为寻找更多慢性炎症治疗的靶点提供有力依据.随着先进的分子生物学以及其他技术的应用,对IL-23/IL-23受体的作用将会有更多更深入的认识,为一些相关疾病的发病机制和治疗手段的研究提供理论基础.     

IL-21与COPD发病机制的研究进展

IL-21是近年来发现的一种细胞因子,主要由活化的 CD4+T 细胞产生,在 Th17细胞中大量分泌,IL-21与其受体结合后,参与免疫应答与炎症反应.COPD是一种由吸烟所诱发的 T 细胞介导的炎症及自身免疫性的疾病.COPD的发病机制复杂,其中免疫失衡在 COPD发生发展中起着重要作用,多种细胞因子的变化与 COPD有关,IL-21就是其中的一种.本文就 IL-21与 COPD 的气道炎症、肺气肿、肺动脉高压的发病机制的研究作一综述.     

Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells

Purpose Tumor-derived exosomes (TEX) have been proposed as a new kind of cancer vaccine; however, their in vivo antitumor effects are not satisfactory. In order to further improve the efficacy of vaccination with TEX, we investigated whether interleukin-2 (IL-2) genetic modification of tumor cells can make IL-2 presence in the exosomes, thus increasing antitumor effects of the TEX. Methods E.G7-OVA tumor cells expressing Ovalbumin (OVA) as a tumor model antigen were used to prepare TEX by serial centrifugation and sucrose gradients ultracentrifugation. To demonstrate their antitumor effects, IL-2-containing exosomes (Exo/IL-2) were injected subcutaneously into C57BL/C mice: either bearing tumor or followed by tumor inoculation. Results We found IL-2 within those exosomes as detected by both ELISA and Western blot. Vaccination with these Exo/IL-2 could induce antigen-specific Th1-polarized immune response and Cytotoxic T lymphocytes (CTL) more efficiently, resulting in more significant inhibition of tumor growth. CD8⁺ T cells are the main effector cells, however, CD4⁺ T cells, and NK cells are also involved in the induction of antitumor response of this approach. Conclusions Our results demonstrate that IL-2 genetic modification of tumor cells can make the TEX contain IL-2 with the increased antitumor effects, representing a promising way of exosome-based tumor vaccine. The first two authors contributed equally to this work.     

Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma

AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.     

Th2／Th17细胞群与支气管哮喘机制研究

支气管哮喘（简称哮喘）是一种由多种细胞（如嗜酸粒细胞、肥大细胞、T淋巴细胞、中性粒细胞和气道上皮细胞等）和细胞组分参与的气道慢性炎症性疾病。经典的Th1／Th2细胞失衡被认为是过敏性哮喘的主要发病机制,Th17／IL-17轴被证实与重症哮喘、激素抵抗型哮喘、以中性粒细胞浸润为主的哮喘有关。近年来研究发现,机体内存在一种不同于目前已知的Thl、Th2、Thl7、Th9等的新型CD4＋T细胞,被称为Th2／Th17双表型记忆性CD4＋T细胞群（简称Th2／Th17细胞群）。在哮喘发病机制的探讨中发现,Th2／Th17细胞群既能分泌Th2表型细胞因子IL-4、IL-5、IL-13,也可以分泌Th17型细胞因子IL-17、IL-8、IL-22等;且在不同的微环境下发生不一样的生物学效应,这显示了Th2／Th17细胞群可能在哮喘发生发展（特别是重症哮喘）及各亚型相互转化过程中起着决定性作用。现就Th2／Th17细胞群的生物学功能及其与哮喘的相关性进行如下综述。     

急性日本血吸虫病与血清白介素?33的关系研究

目的 目的 检测急性日本血吸虫病患者外周血血清白介素?33 （IL?33） 水平, 探讨IL?33在急性日本血吸虫病疾病进展中的作用。方法 方法 选择来自湖区的4例急性日本血吸虫病患者和来自非疫区的15例对照者作为研究对象, 收集人口学资料并采集肘静脉血。采用酶联免疫吸附试验检测所有研究对象的外周血血清IL?33水平。应用Stata 10.0软件进行数据的统计学分析。 结果 结果 急性日本血吸虫病患者血清IL?33水平为517.33 （334.65,1 056.88）pg/ml, 显著高于对照者血清IL?33 水平1.66 （1.66,6.35）pg/ml （Z= -3.207,P = 0.001）。急性日本血吸虫病患者血清IL?33水平与外周血嗜酸粒细胞计数、 患者感染时长的相关系数均为0.8, 相关系数均无统计学意义 （P = 0.2）。结论 结论 IL?33在急性日本血吸虫病患者血清中显著升高, 在日本血吸虫病急性期发挥了促进炎症作用, 并可能在患者感染日本血吸虫后7~9周参与启动Th2型免疫应答。     

白介素25与支气管哮喘关系的研究进展

白介素25(IL-25)是新近发现的IL-17家族的新成员之一,其主要由活化的Th2细胞和肥大细胞所分泌.IL-25能够促进IL-4、IL-5及IL-13分泌、增强Th2型免疫应答、导致嗜酸粒细胞的浸润,在哮喘的发病中起着重要作用.     

Central role of interleukin-15 in human immunodeficiency virus (HIV)-infected patients with visceral leishmaniasis

To evaluate clinical and immunological parameters, interleukin (IL)-15 production and outcome of patients with visceral leishmaniasis (VL), including HIV positive patients, we analyzed 48 cases of VL. Clinical manifestations and response to therapy were similar in VL/HIV- and VL/HIV+ patients. However, relapses were more frequent in patients with HIV infection. Low levels of IL-15 concentrations were found in HIV+ patients without VL. These levels were comparable to concentrations obtained in healthy donors. We found a relationship between response to therapy and IL-15 levels. We found increased levels of IL-15 in VL/HIV- and VL/HIV+ patients with clinical and parasitological response to therapy. Our data demonstrate that VL in HIV-infected patients occurs in subjects with severe immunodeficiency and presents high rate of relapses. Low levels of IL-15 in illness patients and restored production in cured persons suggest that this cytokine could play a central role in immune responses during Leishmania/HIV co-infection.     

Nitric oxide modulates interleukin-1beta and tumour necrosis factor-alpha synthesis, and disease regression by alveolar macrophages in pulmonary tuberculosis

Pretreatment with nitric oxide synthase (NOS) inhibitors profoundly increases mortality, bacterial burden and pathological tissue damage in mice infected with Mycobacterium tuberculosis. Nitric oxide (NO) production is enhanced in alveolar macrophages (AM) of tuberculosis (TB) patients. Interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha released from AM are involved in the immune response to mycobacterial infection. The aim of the present study was to examine whether NO is implicated in IL-1beta and TNF-alpha synthesis by AM and related to the resolution of disease activity in TB patients. Purified AM were retrieved by bronchoalveolar lavage from TB patients and normal subjects, and cultured in the presence or absence of a NO inhibitor, NG-monomethyl-L-arginine (L-NMMA). The release of IL-1beta and TNF-alpha, and their mRNA expression were determined by enzyme-linked immunosorbent assay (ELISA) and northern analysis, respectively. The level of nitrite released into the culture medium was determined. The rate of disease regression was evaluated by serial chest radiography. The release of nitrite, IL-1beta and TNF-alpha was much greater from AM of TB patients than normal subjects. NG-monomethyl-L-arginine inhibited the production of nitrite as well as IL-1beta and TNF-alpha in TB patients. The mRNA expression for IL-1beta and TNF-alpha was upregulated in TB patients and was depressed by L-NMMA. Immunocytochemistry using a monoclonal antibody against nuclear factor-kappaB (NF-kappaB) subunit p65 showed NF-kappaB was highly expressed and translocated to the nuclei of AM in TB patients, and was inhibited by L-NMMA. An inhibition of NF-kappaB by pyrrolidine dithiocarbamate attenuated IL-1beta and TNF-alpha synthesis. More generation of NO from cultured AM increased the disease regression in TB patients. We conclude that the enhanced NO generation by AM of TB patients may play an autoregulatory role in amplifying the synthesis of pro-inflammatory cytokines, probably through the activation of NF-kappaB. Nitric oxide may also play an important role in resistance to M. tuberculosis infection.