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Active immunotherapy of allergic asthma with a recombinant human interleukin-5 protein as vaccine in a murine model

Chinese Medical Journal 2007年第17期120卷 1517-1522页

作者： TAN Guang—hong WANG Cai-chun HUANG Feng-ying WANG Hua HUANG Yong—hao LIN Ying-ying Hainan Provincial Key Laboratory of Tropical Medicine HainanMedical College Haikou 571101 China Department of Paediatrics Affiliated Hospital of Hainan Medical College Haikou 571101 China . Department of Respiratory Diseases Affiliated Hospital of Hainan Medical College Haikou 571101 China

Background Eosinophils are highly related to allergic asthma inflammation. interleukin （IL）-5 is the major chemokine of eosinophils, inhibition of the activity of IL-5 thus seems to be a potential approach to asthma therapy. The current study was performed to determine whether a recombinant human IL-5 protein as a xenogeneic vaccine has the capability of inducing anti-asthma activities. Methods Recombinant human IL-5 was used as a protein vaccine. Mouse asthma model was established to observe the anti-asthma activities. Lung histology was observed; eosinophils in blood and bronchoalveolar lavage were stained and counted, Airway hyperresponsiveness was determined by whole body plethysmograph. Antibody characters and cytokines were detected with enzyme linked immunosorbent assay （ELISA） and Western blot assay. Results Vaccination with recombinant human IL-5 protein as vaccine significantly reduced airway inflammation and airway hyperresponsiveness, and shifted the cytokine production from Th2 （IL-4） to Thl （INF-γ） in mice allergic-asthma model. Immunization with recombinant human IL-5 protein vaccine bypassed the immunological tolerance and induced production of polyclonal antibodies that were cross-reactive with murine IL-5. Conclusions Active immunization with xenogeneic homologous IL-5 may be a possible therapeutic approach to the treatment of asthma and potentially of other eosinophilic disorders.

关键词： asthma interleukin-5 eosinophil recombinant protein vaccine airway hyperresponsiveness

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Role of Activator Protein-1 in the Transcription of interleukin-5 Gene Regulated by Protein Kinase C Signal in Asthmatic Human TLymphocytes

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2005年第2期25卷 147-150页

作者：郭琦徐永健张珍祥 Department of Respiratory Medicine Tongji Hospital Tongji Medical College HuazhangUniversity of Science and Technology Wuhan 430030 China

Summary: In order to explore the role of activator protein-1 (AP-1) in the transcription of interleukin-5 (IL-5) gene regulated by protein kinase C (PKC) signal in peripheral blood T lymphocytes from asthmatic patient, T lymphocytes were isolated and purified from peripheral blood of each asthmatic patient. The T lymphocytes were randomly divided into 4 groups: group A (blank control), group B (treated with PKC agonist phorbol 12-myristate 13-acetate (PMA)), Group C (treated with PMA and AP-1 cis-element decoy oligodeoxynucleotides (decoy ODNs)), and group D (treated with PMA and AP-1 mutant decoy ODNs). The ODNs were transfected into the T cells of group C and D by cation liposome respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to assess IL-5 mRNA expression, and electrophoretic mobility shift assays (EMSA) for the activation of AP-1. The results showed that the activation of AP-1 (88 003.58±1 626.57) and the expression of IL-5 mRNA (0.8300±0.0294) in T lymphocytes stimulated with PMA were significantly higher than these in blank control (20 888.47±1103.56 and 0.3050±0.0208, respectively, P5±0.0171 respectively) of T lymphocytes stimulated with PMA and AP-1 decoy ODNs were significantly inhibited, as compared with group B (P5±0.0222, respectively) in T lymphocytes stimulated with PMA and AP-1 mutant decoy ODNs did not exhibit significant changes, as compared with group B (P>0.05). The significant positive correlation was found between the activation of AP-1 and the expression of IL-5 mRNA (P5 gene in asthmatic T lymphocytes. This suggests the activation of PKC/AP-1 signal transduction cascade of T lymphocytes may play an important role in the pathogenesis of asthma.

关键词： protein kinase C activator protein-1 signal transduction bronchial asthma interleukin-5 cis-element decoy oligodeoxynucleotides

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interleukin (IL) 5 levels and eosinophilia in patients with intestinal parasitic diseases

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World Journal of Gastroenterology 2004年第24期10卷 3643-3646页

作者： Sebnem Ustun Nevin Turgay Songul Bayram Delibas Hatice Ertabaklar Department of Gastroenterology School of MedicineUniversity of Ege35100 BornovaIzmirTurkey Department of Parasitology School of MedicineUniversity of Ege35100 BornovaIzmirTurkey Department of Parasitology School of MedicineUniversity of Dokuz EylulIzmirTurkey Department of Microbiology School of MedicineUniversity of Aydin MenderesAydinTurkey

AIM:Intestinal parasitic diseases are commonly accompanied with diarrhoeal symptoms and allergic *** occurs as a result of IL-5 synthesized from Th2 cells during allergic ***-5 acts as a factor activating eosinophils. The aim of this study was to compare the IL-5 cytokine measurements in serum samples and cell *** also to compare eosinophilia observed in helminth infections and protozoon infections accompanied with allergy. METHODS:Twenty-three patients who presented with diarrhoeal symptoms and allergic complaints were tested positive for intestinal parasites,as well as 21 controls with allergic complaints who did not have any intestinal parasites were included in this ***-5 production in in vitro cell cultures prepared by using phytohemaglutinin (PHA) to stimulate peripheral blood mononuclear cells (PBMC) obtained from the blood samples taken from these patients were compared with the IL-5 level in ***, the IL-5 production in protozoon and helminth infections was also *** eosinophil values in 1 mm^3 of blood were calculated by means of peripheral smear in both groups within the scope of the study. RESULTS:Parasites such as helminth detected in 15 (65.2%) and protozoon in 8 (34.8%) of the patients were included in this *** regards the values of the sera in both patients with parasite infection and controls,the IL-5 production was found to be higher in the cell culture supernatant (P5).When the IL-5 level of the patients with helminth parasites was compared with that of those with protozoon,it was determined that the IL-5 level in serum was more significant in the patients with protozoon than in those with helminth (P5).In the study group,the patients were found to have parasites, the percentage of eosinophil was 7.0% compared to 6.5% in the control ***,there was no significant difference between the eosinophil values (P>0.05). CONCLUSION:It was found that IL-5 cyto

关键词： Adult Cells, Cultured Diarrhea Eosinophilia Female Helminthiasis Humans Hypersensitivity interleukin-5 Male Middle Aged Protozoan Infections Th2 Cells

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In situ hybridization for interleukin 4 and 5 messenger RNA in asthma

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中华内科杂志 1998年第Z1期37卷 32-32页

作者：赵如冰孙永昌高天祥 DepartmentofHealthCareandEpidemiology SchoolofPublicHealthBeijingMedicalUniversityBeijingChina

Objective To examine whether or not peripheral blood mononuclear cells (PBMCs) from steroid-resistant (SR) asthmatics express different profiles of cytokines from their steroid-sensitive (SS) counterparts, particularly after treatment with steroid. Method In situ hybridization was used to detect the mRNA from *** PBMCs from SR patients did not differ significantly from those of SS in the expression of interleukin (IL-4) mRNA or IL-5 mRNA (P＞0.05). There was no difference in the number of PBMCs expressing IL-4 mRNA and IL-5 mRNA (P＞0.05) between incubation in the absence or presence of dexamethasone (DXM, 10-7mol/L) in SR. SS patients had a significant decrease in the number of PBMCs expressing IL-4 mRNA and IL-5 mRNA (P＜0.01) after culturing in the presence of DXM when compared with incubation in media alone. Conclusion Our findings indicate that SR asthma is associated with a dysregulation of the expression of the genes encoding for IL-4 and IL-5.

关键词： In situ hybridization Asthma interleukin-4 interleukin-5

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抗白细胞介素5抗体治疗支气管哮喘疗效与安全性的荟萃分析

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中华结核和呼吸杂志 2017年第11期40卷 835-844页

作者：顾永丽庞婕宋甲富程聪孙增先连云港市第一人民医院药剂科江苏222001 连云港市第一人民医院呼吸内科江苏222001

目的系统评价抗IL-5抗体治疗支气管哮喘（哮喘）患者的疗效及安全性.方法根据特定中英文检索词检索PubMed、EMbase、Springer、Ovid、Cochrane Library、***和CNKI、万方数据库的所有相关临床随机对照研究（RCT）,检索时间截至2017年2... 详细信息

目的系统评价抗IL-5抗体治疗支气管哮喘（哮喘）患者的疗效及安全性.方法根据特定中英文检索词检索PubMed、EMbase、Springer、Ovid、Cochrane Library、***和CNKI、万方数据库的所有相关临床随机对照研究（RCT）,检索时间截至2017年2月.同时检索纳入文献的参考文献,并逐个进行质量评价和资料提取.采用RevMan5.3软件进行统计学分析.结果共纳入20篇文献,23个RCT,共计6406例患者.荟萃分析结果显示,抗IL-5抗体可明显降低哮喘急性加重的发生率[RR =0.66,95％ CI（0.59,0.73）],改善患者FEV1 [MD =0.10,95％ CI （0.07,0.13）]、FEV1占预计值％[MD =3.90,95％ CI（1.86,5.95）]和哮喘生命质量问卷（AQLQ）评分[MD=0.24,95％ CI（0.16,0.32）],且降低了不良事件的发生风险[OR =0.71,95％ CI（0.58,0.87）].结论抗IL-5抗体可降低哮喘患者急性加重的发生率,并改善患者肺功能及生命质量,且具有较好的耐受性.

关键词：白细胞介素5 抗体哮喘 Meta分析 interleukin-5

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Effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD_(34)^+ hematopoietic cells in bone marrow of asthmatic mice

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Chinese Medical Journal 2004年第4期117卷 592-597页

作者：毛辉殷凯生王曾礼李富宇Department of General Surgery West China Hospital 张希龙刘春涛雷松Department of Tumor Biological Therapy West China Hospital Department of Respiratory Medicine Department of Respiratory Medicine West China Hospital

BACKGROUND: Corticosteroids remain the most effective therapy available for asthma. They have widespread effects on asthmatic airway inflammation. However, little is known about the effects of corticosteroids on the production of bone marrow inflammatory cells in asthma. This study observed the effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD34+ hematopoietic cells, so as to explore the possible effectiveness of a bone marrow-targeted anti-inflammatory strategy. METHODS: Balb/c mice were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. For two consecutive weeks, asthmatic mice were challenged with OVA while being given either prednisone, montelukast, prednisone plus montelukast, or sterile saline solution. The mice were killed 24 hours after the last challenge with OVA, and bronchoalveolar lavage fluid (BALF), peripheral blood, and bone marrow were collected. Eosinophils in peripheral blood and BALF, and nucleated cells in BALF, peripheral blood, and bone marrow were counted. The percentages of CD34+ cells, CD4+ T lymphocytes and CD8+ T lymphocytes among nucleated cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect expression of CD34 and interleukin (IL)-5Ralpha mRNA (CD34+ IL-5Ralpha mRNA+ cells) among bone marrow hematopoietic cells. RESULTS: Compared with the sterile saline solution group, the number of eosinophils in BALF and peripheral blood, CD34+ cells in peripheral blood and bone marrow, and CD34+ IL-5Ralpha mRNA+ cells in bone marrow of mice from the prednisone and prednisone plus montelukast groups were significantly lower (P

关键词： Acetates Animals Antigens, CD34 Asthma Cell Count Hematopoietic Stem Cells Immunohistochemistry In Situ Hybridization interleukin-5 Male Mice Mice, Inbred BALB C Prednisone Quinolines Research Support, Non-U.S. Gov't

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Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury

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Bioactive Materials 2023年第5期23卷 369-382页

作者： Dongjian Han Fuhang Wang Zhentao Qiao Bo Wang Yi Zhang Qingjiao Jiang Miaomiao Liu Yuansong Zhuang Quanxu An Yan Bai Jiahong Shangguan Jinying Zhang Gaofeng Liang Deliang Shen Department of Cardiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Key Laboratory of Cardiac Injury and Repair of Henan Province ZhengzhouChina Department of Vascular and Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China School of Basic Medical Sciences Henan University of Science and TechnologyLuoyang471023HenanChina

Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac ***-5(IL-5)plays an essential role in developing eosinophils(EOS),which are beneficial for the resolution of ***,the proangiogenic properties of IL-5 also contribute to tissue healing following ***,targeted delivery of IL-5 is an innovative therapeutic approach for treating *** has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug *** this study,we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic *** administration of neutrophil membrane-camouflaged nanoparticles(NM-NPIL-5)in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium,thereby limiting adverse cardiac remodeling after *** results also demonstrated that the NM-NPIL-5 could serve as neutrophil“decoys”to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their“parent”***,the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac *** findings provided a promising cardiac detoxification agent for acute cardiac injury.

关键词： Biomimetic nanoparticles interleukin-5 Eosinophils Angiogenesis Myocardial infarction

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Mepolizumab induced palmoplantar psoriasis:A case report

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World Journal of Clinical Cases 2023年第26期11卷 6154-6158页

作者： Fabio Artosi Laura Diluvio Martina Vultaggio Elena Campione Luca Bianchi Department of Systems Medicine University of Rome“Tor Vergata”Rome 00133Italy Department of Dermatology Dermatology UnitPoliclinico Tor VergataRome 00133Italy Department of Dermatology University Roma Tor VergataRome 00133Italy

BACKGROUND Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation,at least in the initial stages,of T helper(Th)-2 Lymphocytes,the related cytokine axis,and B lymphocytes with antibody *** is conversely a pathology resulting from a recruitment of Th-17 and Th-1 lymphocytes,after an initial role of innate *** is a humanized monoclonal antibody directed against interleukin(IL)-5,a central cytokine in the Th-2 axis,therefore involved in the pathogenesis of *** authors have described the appearance of psoriatic lesions in patients with asthma or atopic dermatitis following the therapy with dupilumab,a monoclonal antibody that blocks the interleukin(IL)-4,another Th-2 *** SUMMARY We present the case of a 59-year-old patient who developed psoriasiform lesions on the palms after mepolizumab therapy for asthma,for the activation of the parallel cytokine cascade after the blockade of *** successfully treated the patient with a topical calcipotriol and betamethasone *** We should investigate with further attention the possible impact on the human immunological ecosystem put in place by the inhibition of the activity of individual inflammatory mediators,so as to be able to recognize the initial adverse effects early.

关键词： Psoriasis interleukin-5 Mepolizumab Asthma Immunology Case report

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哮喘患儿血清白细胞介素-5和IgE与肺功能的相关性研究

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山西医药杂志 2014年第7期43卷 754-756页

作者：陈晓锐彭俊旭安正红郑华李鹤中国人民武装警察部队广东省边防总队医院儿科深圳518029 深圳市福田区人民医院麻醉科

目的检测支气管哮喘患儿外周血白细胞介素(IL)-5、总IgE(TIgE)和肺功能水平,探讨IL-5、TIgE与肺功能水平及支气管哮喘之间的相关性。方法选取35例门诊随诊的哮喘缓解期患儿作为哮喘组,30名同期健康体检儿童作为健康对照组,2组儿童均于... 详细信息

目的检测支气管哮喘患儿外周血白细胞介素(IL)-5、总IgE(TIgE)和肺功能水平,探讨IL-5、TIgE与肺功能水平及支气管哮喘之间的相关性。方法选取35例门诊随诊的哮喘缓解期患儿作为哮喘组,30名同期健康体检儿童作为健康对照组,2组儿童均于清晨空腹取外周静脉血1.0mL制备血清,应用双抗体夹心酶联免疫吸附试验(ELISA)法测定2组儿童血清IL-5、TIgE,并行肺功能检测。结果哮喘组患儿血清IL-5、TIgE水平均较健康对照组升高,差异有统计学意义(t=6.84、21.63,P5%肺活量时呼气流量(FEF25%)、用力呼出50%肺活量时呼气流量(FEF50%)哮喘组较健康对照组水平明显下降(t=-2.258、-2.428,P5),而第1秒用力呼气容积占用力肺活量的比值(FEV1/FVC%)差异无统计学意义;IL-5与FEV1/FVC%、FEF25%、FEF50%无相关性,TIgE与FEV1/FVC%、FEF25%、FEF50%呈负相关(r=-0.534、-0.392、-0.394,P5)。结论哮喘患儿体内存在Th1/Th2免疫失衡,IL-5和TIgE参与气道高反应与呼吸道重塑的病理生理过程,TIgE即使在哮喘缓解期也仍然和肺功能密切相关,可以成为辅助判定哮喘严重程度的参考指标。

关键词：哮喘白细胞介素-5 肺功能测定儿童 interleukin-5

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Antisense oligonucleotides-induced local blockade of T-bet expression leads to airway inflammation in rats

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Acta Pharmacologica Sinica 2006年第5期27卷 561-567页

作者： Gang WANG~2 Chun-tao LIU~(3,4) Zeng-li WANG~3 Li-li JIANG~5 Cun-liang YAN~6 Feng-min LUO~3 ~2Department of Integrated Traditional Chinese and Western Medicine.West China Hospital.Sichuan University,Chengdu 610041,China.~3Department of Respiratory Medicine,West China Hospital,Sichuan University.Chengdu 610041.China ~5Department of Pathology,West China Hospital.Sichuan University,Chengdu 610041,China:~6Department of Laboratory Medicine.Shenzhen Hospital,Peking University.Shenzhen 518036,China DepartmentoflntegratedTraditionalChineseandWesternMedicine WestChinaHospitalSichuanUniversityChengdu610041China DepartmentofRespiratoryMedicine WestChinaHospitalSichuanUniversityChengdu610041China

Aim:To explore whether local blockade of T-box expressed in T cells (T-bet)expression in the lungs could lead to airway ***:Twenty-fourrats were randomly divided into 4 groups:saline group,ovalbumin (OVA)-sensi-tized group,nonsense group,and the antisense *** OVA-sensitized ratswere sensitized and challenged with OVA,and the rats in the nonsense andantisense groups were subjected to an aerosol delivery of the nonsense andantisense oligonucleotides (AS-ODN) of T-bet (0.1%,w/v).The levels of inter-feron-γ(IFN-γ),interleukin-4(IL-4),and IL-5 in the bronchoalveolar lavage fluid(BALF) were detected by ELISA,and the mRNA and the protein expression ofT-bet and GATA-3 genes were examined by in situ hybridization and Western blotanalysis,***:The expression of T-bet mRNA and protein in thelungs of the rats in the antisense group were inhibited *** lungs ofthe rats in the antisense and OVA-sensitized groups showed eosinophil and lym-phocyte inflammatory infiltration,and eosinophilia located predominantly aroundthe *** number of GATA-3 mRNA-positive cells and the level of GATA-3protein in the lungs of the rats in the antisense and the OVA-sensitized groupssignificantly *** level of IL-4 and IL-5 in the BALF in the antisenseand OVA-sensitized groups were elevated,but the level of IFN-γ ***:Antisense ODN-induced local blockade of T-bet expres-sion leads to airway inflammation with a selective alteration in patterns of cytokineexpression and recruitment of eosinophil cells similar to that in the OVA-sensitizedanimals.

关键词： airway inflammation antisense oligonucleotides GATA3 transcription factor interferon type Ⅱ interleukin-4 interleukin-5 Tbox expressed in T cells

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