IL-10对哮喘小鼠血清IL-5和IgE的影响

目的:探讨IL-10治疗对哮喘鼠血清IL-5及IgE水平的影响.方法:制备20只小鼠哮喘模型,随机分为治疗组、哮喘组,前者使用IL-10治疗,后者未予治疗,用ELISA双抗体夹心法测定治疗组和哮喘组血清IL-5和IgE的水平.以10只健康小鼠为对照组.结果:与对照组比较,哮喘组IL-5和IgE水平较高,差异均有统计学意义(P＜0.05);经IL-10治疗后,治疗组的血清IL-5、IgE的水平明显低于哮喘组水平,其差异有统计学意义(P＜0.05);治疗组治疗后IL-5和和IgE检测值与正常组水平差异无统计学意义(p＞0.05).结论:IL-10能够降低哮喘小鼠血清的IL-5和IgE水平.     

IL-5和IL-25在变应性鼻炎患者血清中的表达及临床意义

<正>变应性鼻炎(allergic rhinitis,AR)与支气管哮喘(bronchial asthma)均为呼吸道炎症,70%~80%的哮喘患者均伴有变应性鼻炎,二者在病因、发病机制等方面具有相似性。目前认为,白介素-5(interleukin-5,IL-5)在Ι型变态反应中起关键作用;在哮喘患者研究中,白介素-25(interleukin-25,IL-25)可促     

抗IL-5纳米抗体筛选及活性检测

白介素-5(IL-5)是一种同源二聚体细胞因子,是嗜酸性粒细胞(eosinophilic, EOS)增殖、活化和成熟的重要调节因子。抗IL-5单克隆抗体能阻断IL-5与IL-5受体亚单位α(IL-5Rα)结合,已成功用于治疗嗜酸性粒细胞哮喘。目前上市的单克隆抗体药物需要反复注射给药,严重影响了患者的依从性,而且注射给药的全身暴露率高。为获得适合吸入给药的抗体,在羊驼天然库中通过3轮淘选,挑取单克隆通过Phage ELISA初筛,共获得461个阳性克隆,其中50个为序列独特的分子,最终选择30个分子进行重组表达纯化。通过ELISA结合、ELISA阻断、FACS阻断、TF-1增殖抑制等实验对候选抗体进行体外活性检测,成功获得一个具有阻断IL-5和IL-5Rα结合的纳米抗体AIL-A96-Fc。通过与人和猴IL-5的ELISA结合实验表明,该分子具有良好人猴交叉活性,而且在FACS阻断实验和ELISA阻断实验中,AIL-A96-Fc表现出良好的阻断效果。该开发方法不仅提供了一个靶向IL-5的候选纳米抗体AIL-A96-Fc,也为后续开发更多靶向IL-5的候选纳米抗体提供了指导意义。     

Parasite-Antigen Driven Expansion of IL-5? and IL-5+ Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ

Background

Two different Th2 subsets have been defined recently on the basis of IL-5 expression – an IL-5⁺Th2 subset and an IL-5⁻Th2 subset in the setting of allergy. However, the role of these newly described CD4⁺ T cells subpopulations has not been explored in other contexts.

Methods

To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5⁺IL-4⁺IL-13⁺ CD4⁺ T cells and IL-5⁻IL-4 IL-13⁺ CD4⁺ T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (F_o) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP).

Results

INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced F_o of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the F_o of IL-5⁺Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4⁺IL-5⁻Th2 subpopulation and the levels of parasite antigen – specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGFβ demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased F_o of both Th2 subsets.

Conclusions

Our findings suggest that both IL-5⁺ and IL-5⁻Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes.     

柴胡渗湿汤对哮喘大鼠血清中IL-5 及IL-13 影响的实验研究

目的:观察柴胡渗湿汤对哮喘大鼠血清中IL-5及IL-13含量的影响,探讨柴胡渗湿汤治疗哮喘的作用机制。方法:将84只雄性Wi star大鼠按随机数字表法分为正常对照组、模型对照组、地塞米松组、定喘汤组、柴胡渗湿汤低剂量组、柴胡渗湿汤中剂量组、柴胡渗湿汤高剂量组,每组12只,采用卵蛋白制作大鼠哮喘模型,予相应药物干预。用酶联免疫吸附试验(ELISA)法检测各组大鼠血清中IL-5及IL-13水平。实验数据采用SPSS11.5统计软件进行分析。结果:实验后各组死亡率比较均无差异,P>0.05;模型对照组与正常对照组血清中IL-5及IL-13含量水平有显著差异,表明大鼠哮喘模型存在着血清IL-5及IL-13含量异常增高的病理状态;与模型对照组相比较,各治疗组血清中IL-5及IL-13的含量明显降低,其中尤以地塞米松组、柴胡渗湿汤中剂量组和柴胡渗湿汤高剂量组的作用更明显。结论:柴胡渗湿汤治疗哮喘的作用机制与降低IL-5及IL-13的水平有关;上述作用具有一定的量效关系,但并不因给药剂量的增加而增加。     

吸烟对下呼吸道诱导痰中 IFN-γ、IL-4、IL-5表达的影响

目的探究吸烟对下呼吸道诱导痰中干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)和白细胞介素-5(IL-5)表达的影响。方法采用酶联免疫吸附法检测2016年3月-2017年3月沈阳医学院附属第二医院收治的下呼吸道感染患者88例(其中吸烟者44例作为观察组,非吸烟者44例作为对照组)、健康体检者76例(其中吸烟者34例作为观察组,非吸烟者42例作为对照组)诱导痰中IFN-γ、IL-4和IL-5的表达,并对结果进行数据分析。结果 (1)健康体检者中吸烟者与非吸烟者相比,吸烟者IL-4、IL-5水平显著上升,IFN-γ水平显著下降(P0.05);(2)下呼吸道感染患者中吸烟者与非吸烟者相比,吸烟者IL-4、IL-5水平显著上升,INF-γ水平显著下降(P0.05)。结论吸烟与下呼吸道诱导痰中IL-4、IL-5和IFN-γ的水平有关,吸烟可使下呼吸道诱导痰中IL-4、IL-5水平升高而IFN-γ的水平下降。     

5%环孢菌素霜对银屑病合并代谢综合征患者血清IL-17 及IL-18 水平的 影响

目的:探讨5%环孢菌素霜对银屑病合并代谢综合征患者外周血IL-17、IL-18水平及PASI评分的影响。方法:选择我院收治的寻常型银屑病合并代谢综合症患者68例,分为实验组和对照组。对照组予以复方甘草酸苷和卡泊三醇治疗,实验组在此基础上加用制备好的5%环孢菌素霜,观察并比较两组患者治疗前后外周血IL-17及IL-18水平的变化情况以及血压、空腹血糖、血脂及PASI评分结果。结果:与治疗前比较,两组患者治疗后IL-17及IL-18水平、血压、FPG、TG及PASI评分均显著降低,而HDL-C明显升高,差异均具有统计学意义(P0.05);与对照组比较,实验组治疗后IL-17及IL-18水平、血压、FPG、TG及PASI评分较低,而HDL-C较高,差异均具有统计学意义(P0.05)。结论:5%环孢菌素霜辅助治疗可调节银屑病合并代谢综合征患者外周血IL-17、IL-18水平,降低其PASI评分,改善患者机体代谢紊乱状态,对银屑病合并代谢综合症有显著临床疗效。     

肺炎支原体感染小鼠体内IL-6、IFN-γ、IL-5的水平 及克拉霉素的影响

目的：研究肺炎支原体感染小鼠血清及支气管肺泡灌洗液中细胞因子的水平,了解克拉霉素治疗对细胞因子的影响。方法： 将昆明小鼠分为感染组、正常组及药物治疗组,建立小鼠肺炎支原体感染模型成功后,药物组用克拉霉素（6 g·kg-1·d-1）进行治疗, 连续5 天。在肺炎支原体感染模型建立后的第8 天,检测三组小鼠的血清及支气管肺泡灌洗液中IL-6、IFN-γ、IL-5 水平。结果： 相比较于正常组,感染组小鼠支气管灌洗液和血清中的IL-6、IFN-γ、IL-5 均显著升高(P ＜0.05)。而克拉霉素的使用能使IL-6、 IFN-γ降低(P ＜0.05),但对IL-5 水平无影响。结论：肺炎支原体感染使小鼠IL-6、IFN-γ、IL-5 水平增高,克拉霉素治疗有一定疗 效。     

肺炎支原体感染小鼠体内IL-6、IFN-γ、IL-5的水平及克拉霉素的影响

目的：研究肺炎支原体感染小鼠血清及支气管肺泡灌洗液中细胞因子的水平,了解克拉霉素治疗对细胞因子的影响。方法：将昆明小鼠分为感染组、正常组及药物治疗组,建立小鼠肺炎支原体感染模型成功后,药物组用克拉霉素（6g·kg^-1·d^-1）进行治疗,连续5天。在肺炎支原体感染模型建立后的第8天,检测三组小鼠的血清及支气管肺泡灌洗液中IL-6、IFN-γ、IL-5水平。结果-相比较于正常组,感染组小鼠支气管灌洗液和血清中的IL-6、IFN-γ、IL-5均显著升高（P〈0．05）。而克拉霉素的使用能使IL-6、IFN-γ降低（P〈0．05）,但对IL-5水平无影响。结论：肺炎支原体感染使小鼠IL-6、IFN-γ、IL-5水平增高,克拉霉素治疗有一定疗效。     

Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection

The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg–Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk’s lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg–Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI.     

IL-1，IL-6，IL-8 与胃癌的关系

胃癌是常见的恶性肿瘤之一,在我国其发病率居各类肿瘤前列,导致的死亡人数占所有肿瘤的四分之一,而且每年有近40万新增的胃癌病人,但是其早期诊断率低于20%,胃癌已经成为危害人民健康的最严重的疾病之一。白细胞介素(interleukin,IL)作为在白细胞或免疫细胞间相互作用的淋巴因子,不仅在介导T、B细胞活化、增殖与分化以及炎症反应中起着重要作用,近年来,越来越多的学者发现其与肿瘤的发生及发展也有着密不可分的联系。目前为止,已经发现了29种白细胞介素,分别被命名为IL-1~IL-29,它们各自承担着相应的使命。国内外大量实验及文献表明,IL-1,IL-6,IL-8和胃癌有着密切的关系,这对于胃癌的早期诊断及治疗提出了新的思路,进而提高胃癌的早期诊断率,改善胃癌的治疗状况。本文对IL-1,IL-6,IL-8的来源、分子结构及受体方面进行简要概述,同时阐述了其生物学特性及与胃癌的关系。     

IL-32γ induces chemotaxis of activated T cells via dendritic cell-derived CCL5

Interleukin (IL)-32 has been associated with a variety of inflammatory diseases including rheumatoid arthritis, vasculitis and Crohn’s disease. We have previously reported that IL-32γ, the IL-32 isoform with the highest biological activity, could act as an immune modulator through regulation of dendritic cell (DC) functions in immune responses. Cell locomotion is crucial for induction of an effective immune response. In this study, we investigated the effect and underlying mechanisms of IL-32γ on recruitment of T cells. IL-32γ upregulated the expression of several chemokines including CCL2, CCL4, and CCL5 in the DCs. In particular, IL-32γ significantly increased CCL5 expression in a dose-dependent manner. Treatment with JNK and NF-κB inhibitors suppressed IL-32γ-induced CCL5 expression in DCs, indicating that IL-32γ induced CCL5 production through the JNK and NF-κB pathways. Furthermore, supernatants from IL-32γ-treated DCs showed chemotactic activities controlling migration of activated CD4⁺ and CD8⁺ T cells, and these activities were suppressed by addition of neutralizing anti-CCL5 antibody. These results show that IL-32γ effectively promotes migration of activated T cells via CCL5 production in DCs. The chemotactic potential of IL-32γ may explain the pro-inflammatory effects of IL-32 and the pathologic role of IL-32 in immune disorders such as rheumatoid arthritis.     

IL-4、5-HT在过敏性休克死亡豚鼠脏器中的表达及其意义

目的寻找法医学鉴定过敏性休克死亡的病理形态学诊断指标。方法利用组织芯片技术采用免疫组化方法（SP法）检测42只过敏性休克豚鼠（实验组28只,空气栓塞组7只,对照组7只）死后0,6,12,24h4个时间点的心、肝、肺、肾、脾、胃、肠、气管及扁桃体组织中的IL-4和5-HT的表达情况。结果（1）IL-4的表达：实验组肺、气管及胃组织呈阳性表达,并以0、6h表达最强,各时间点的表达强度有统计学意义,P〈0．01;肠组织呈弱阳性表达,各时间点的表达强度无统计学意义,P〉0．05;实验组其它脏器、空气栓塞组及对照组所有脏器均无表达。（2）5-HT的表达：实验组肠组织呈弱阳性表达,各时间点的表达强度无统计学意义,P〉0．05;实验组其它脏器、空气栓塞组及对照组所有脏器均无表达。结论免疫组化方法检测IL-4的表达,可望作为鉴定过敏性休克死亡的病理形态学诊断参考指标;肺、气管及胃组织IL-4表达以0、6h表达最强,提示法医学鉴定过敏性休克死亡应尽早尸检。     

COPD大鼠肺组织中Muc5ac和IL-13的相关性研究

目的:研究慢性阻塞性肺病(COPD)大鼠气道粘蛋白Muc5ac和白介素13(IL-13)的表达及其相关性.方法:20只wistar雄性大鼠随机分为对照组和COPD组.正常组8只,COPD组12只,分别用免疫组化法测定肺组织Muc5ac和IL-13的表达.结果:Muc5ac和IL-13蛋白表达主要位于气道上皮细胞,细胞胞浆呈棕黄色.COPD组大鼠肺组织IL-13和Muc5ac的表达均高于正常组(P均＜0.05).结论:IL-13是引起粘液分泌的重要因子,它可能上调Muc5ac的表达.     

IL-39:IL-12家族的新成员

白细胞介素-39(interleukin,IL-39)是最近发现的IL-12家族新成员,由IL-23p19和EB病毒诱导基因3两个亚基组成。它主要由脂多糖刺激的B细胞和狼疮小鼠体内活化的GL7~+B细胞产生,IL-23R/gp130为其受体,在狼疮小鼠体内通过激活信号转导与转录激活因子1(STAT1)/STAT3信号通路介导炎症反应。因此,深入研究IL-39的结构、信号通路以及生物学功能,对系统性红斑狼疮和其它自身免疫性疾病的治疗具有重要价值。     

孟鲁司特钠对过敏性鼻炎患者血清IL-5和IL-10水平的影响及安全性分析

目的:分析孟鲁司特钠对过敏性鼻炎患者血清白细胞介素-5(IL-5)及白细胞介素-10(IL-10)水平的影响及安全性。方法:选择我院2015年10月~2016年10月收治的106例过敏性鼻炎患者,按不同治疗方式分作对照组与研究组,每组53例。对照组选用氯雷他定片治疗;研究组在对照组基础上加以孟鲁司特钠治疗。观察并比较两组患者的临床疗效、治疗前后血清IL-5及IL-10水平变化、症状及体征积分及不良反应发生情况。结果:研究组总有效率(94.33%)高于对照组(79.24%)(P0.05)。治疗后,两组血清IL-5,症状及体征积分均显著下降,研究组下降更明显,两组血清IL-10均有显著上升,研究组上升更明显,差异均有统计学意义(P0.05)。两组不良反应发生情况比较,差异无统计学意义(P0.05)。结论:孟鲁司特钠能够调节过敏性鼻炎患者血清炎症因子水平,降低症状积分,且安全性较高。     

IL-7 splicing variant IL-7δ5 induces human breast cancer cell proliferation via activation of PI3K/Akt pathway

Various tumor cells express interleukin 7 (IL-7) and IL-7 variants. IL-7 has been confirmed to stimulate solid tumor cell proliferation. However, the effect of IL-7 variants on tumor cell proliferation remains unclear. In this study, we evaluated the role of IL-7δ5 (an IL-7 variant lacking exon 5) on proliferation and cell cycle progression of human MDA-MB-231 and MCF-7 breast cancer cells. The results showed that IL-7δ5 promoted cell proliferation and cell cycle progression from G1 phase to G2/M phase, associated with upregulation of cyclin D1 expression and the downregulation of p27(kip1) expression. Mechanistically, we found that IL-7δ5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the proliferation and cell cycle progression of MDA-MB-231 and MCF-7 cells induced by IL-7δ5. In conclusion, our findings demonstrate that IL-7δ5 variant induces human breast cancer cell proliferation and cell cycle progression via activation of PI3K/Akt pathway. Thus, IL-7δ5 may be a potential target for human breast cancer therapeutics intervention.     

多发性骨髓瘤骨病患者血清中IL-6和TRACP-5b表达的临床意义

目的:探讨患者血清中白介素-6(Interleukin-6,IL-6)、抗酒石酸盐酸性磷酸酶(Tartrate-resistant acid phosphatase,TRACP-5b)的水平在多发性骨髓瘤骨病(Multiple myeloma bone disease,MBD)发病中的作用及其临床意义。方法:采用双抗体夹心酶联免疫吸附试验法(Enzyme linked immunosorbent assay,ELISA)检测43例MBD患者组及22例MM患者组(无骨损害)及40例健康对照组血清中的IL-6、TRACP-5b的水平,并对检测结果进行统计学分析。结果:MBD患者组血清IL-6、TRACP-5b(27.93±7.45,21.33±5.66)水平较MM患者组(无骨损害)(13.58±4.85,7.23±2.86)、健康对照组(5.65±2.57,6.76±2.65)明显升高,差异有统计学意义(P0.01);Ⅲ期MM患者血清IL-6、TRACP-5b水平(31.92±7.84,24.2±7.86)明显高于I期(11.58±4.85,7.13±2.86)、Ⅱ期(22.45±6.51,14.65±6.76)MM患者,差异有统计学意义(P0.01);MBD患者血清IL-6与血清TRACP-5b水平呈正相关(r=0.915,P0.01)。结论:检测MM患者血清IL-6、TRACP-5b水平可以作为MBD的辅助诊断指标,血清IL-6、TRACP-5b可能参与了MBD的发生和发展。     

IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity

Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β^−/−), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity.