哮喘患者IFN-r/IL-4的失衡及相应肺功能变化

目的观察支气管哮喘患者外周血白介素4及r-干扰素的水平变化及肺功能的关系。方法选取急性发作期哮喘患者组(哮喘组)25例,健康志愿者(对照组)15例。分别留取血标本,同时测定肺通气功能,测定呼吸阻抗。采用ELISA检测上述两组血清中IFN-r/IL-4水平。结果哮喘组IFN-r水平较对照组明显降低(P<0.01);IL-4水平较对照组明显增高(P<0.01);FEV1则明显降低(P<0.01);R5明显升高(P<0.01),直线相关分析表明,哮喘组IFN-r与FEV1呈正相关(r=0.485,P<0.05),与R5呈负相关(r=-0.516,P<0.05),IL-4与FEV1呈负相关(r=-0.493,P<0.05),与R5呈正相关(r=0.528,P<0.05);血清IFN-r与IL-4呈负相关(r=-0.549,P<0.01)。结论哮喘患者体内IL-4过度产生,IFN-r产生不足,使IFN-r/IL-4失衡;IL-4的升高及IFN-r的下降与FEV1下降,R5升高密切相关,表明IFN-r,IL-4在体内对哮喘发病起调节作用,IFN-r/IL-4失衡是哮喘发病的关键因素之一,且与哮喘的病情加重有关。

猪瘟抗体水平与猪细胞因子IFN-r、IL-4的相关分析

目的:分析猪瘟抗体水平低下与猪IFN-r和IL-4细胞因子的表达情况。方法:对母猪进行病毒PCR检测,筛选出无病毒感染、接种过猪瘟疫苗的健康母猪;采用酶联免疫吸附试验检(ELISA)筛选出抗体水平稳定的阴性猪和阳性猪,并分析抗体阳性猪、阴性猪IFN-r和IL-4细胞因子的表达情况。结果:筛选出抗体水平稳定的11头阴性猪和36头阳性猪,CSF抗体阴性猪外周血中IL-4的含量(9.56±1.12)pg/mL高于抗体阳性猪(7.31±0.49)pg/mL,差异显著(P<0.05);而CSF抗体阴性猪外周血中IFN-r的含量(5.59±0.47)pg/mL略高于抗体阳性猪(5.24±0.20)pg/mL,但差异不显著(P>0.05)。结论:说明细胞因子的含量不同在一定程度上能够影响猪瘟抗体水平的高低,可能是导致猪瘟疫苗免疫反应低下的重要原因之一。

Immune Effects of Porcine Interleukin-2,4 on Piglets Using as Immunopotentiator for PCV Inactivated Vaccine

[ Objective] To investigate the combined immunization of porcine circovirus 2 （PCV2） inactivated vaccine with PoIL-2,4. [ Methods] A total of 60 crossbred piglets were randomly divided into three groups, including the test group （ inoculation of 0.5 dose PCV2 inactivated vaccine with 0. 1 mL PoIL-2,4 at 14 and 28 day-old）, the positive control group （inoculation of 0.5 dose PCV2 inactivated vaccine） and the blank control group. [ Results ] The immune organ index, the lymphocyte transformation rates under different ages and the number of leukocytes and lymphocytes in peripheral blood increased significantly in test group, compared with control group. Moreover, the antibody and neutralizing antibody were also significantly higher in test group than that in control group. The clinical symptoms and pathological changes were not found, and the PC72 was not detected in serum and tissue after challenge test in test group, which indicated that the combined immunization of PCV2 inactivated vaccine with PoIL-2,4 significantly improved the lymphocyte transformation rate, effectively prevented the replication of PCV2 in organism, and enhanced the growth performance of piglets.

滋阴清热方对气道高反应性咳嗽患者IL-4、IFN-γ的影响

目的探讨滋阴清热方对气道高反应性咳嗽患者外周血白介素-4(IL-4)、干扰素-γ(IFN-γ)的影响。方法将明确诊断为气道高反应性咳嗽的患者64例,随机分为对照组和治疗组各32例,治疗组给予滋阴清热方治疗,对照组给予孟鲁司特钠片治疗。疗程均为14天。观察患者治疗前后咳嗽症状积分以及外周血IL-4、IFN-γ的变化。结果治疗后,治疗组患者咳嗽症状减轻程度优于对照组(P<0.05);治疗组总有效率(84.4%)高于对照组(71.9%),2组比较差异有统计学意义(P<0.05)。治疗组IL-4下降及IFN-γ升高均较对照组明显(P<0.05)。结论滋阴清热方治疗气道高反应性咳嗽的作用机制可能与降低血中IL-4水平,提高IFN-γ水平,维持Th1/Th2细胞的平衡,从而减轻气道炎症有关。

BCG-DNA对哮喘患者外周血单个核细胞IFN-γ和IL-4产生的作用

目的 :研究免疫活性物质卡介苗基因组 DNA(BCG- DNA)对哮喘患者外周血单个核细胞 (PBMC) IFN- γ和 IL- 4产生的影响。 方法 :分离哮喘患者 PBMC,分别加入 BCG- DNA、地塞米松刺激培养 ,EL ISA检测培养上清中 IFN- γ及 IL- 4含量 ,RT- PCR检测 PBMC IFN-γ m RNA及 IL - 4 m RNA的表达量 ,并与空白对照组相比较。结果 :地塞米松在体外对哮喘患者PBMC产生的 IFN-γ m RNA和蛋白、IL - 4 m RNA和蛋白均有抑制作用 ;BCG- DNA抑制哮喘患者 PBMC IL - 4 m RNA和蛋白的分泌 ,而促进 IFN -γ m RNA和蛋白的分泌 ,与对照组比较差异显著 (P<0 .0 1 ) ,且在体外对 PBMC无毒性。 结论 :BCG-DNA不仅具有和地塞米松相同的下调 IL - 4表达的作用 ,而且还具有地塞米松所没有的诱导 IFN -γ表达的作用 ,利于纠正哮喘患者体内存在的 Th1 / Th2比例失衡状态 。

Study on the Changes of Immune Factors in Different Stages of Non-Small Cell Lung Cancer Chemotherapy

Objective: To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different times after chemotherapy. Changes in CD4+, CD8+, Th17 and IgG, IgM, and IgA levels. Methods: A total of 118 NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy). The effects of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r, CD4+, CD8+ Th17, IgG, IgM and IgA levels in peripheral blood at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed. The changes of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r and the levels of CD4+, CD8+ Th17, IgG, IgM and IgA in peripheral blood were compared at each time point. Results: NKG2D, IL-12, IL-15, IL-18, TNF-a, IFN-r gradually decreased before chemotherapy, one week after chemotherapy, and two weeks after chemotherapy, the difference was statistically significant, but DC cells were not significant Variety. CD4+ and CD8+ both increased significantly, and the levels of Th17, IgG, IgM, and IgA gradually decreased. Conclusion: In the course of chemotherapy, all immune factors except DC cells were significantly decreased compared with those before chemotherapy, and the decrease of immune factors except DC cells was positively correlated with the length of chemotherapy cycle. If additional immunotherapy is needed, it should be carried out in the early stage of chemotherapy.

IL-10 Enhances Promoter Activity of ILT4 Gene and Up-regulates Its Expression in THP-1 Cells

This study examined the effect of IL-10 on immunoglobulin-like transcript (ILT4) expression of human monocytic leukemic cell line THP-1, especially the role of the ILT4 promoter activity.ILT4 promoter area was amplified by PCR, and was cloned into the eukaryotic expressing vector pGL3-Basic.The pGL3-ILTP obtained was tested by double endonuclease digestion and sequencing.Then, the recombinant plasmid was transfected into THP-1 cells by using lipofectamine.After culture with IL-10 for 12 h, the mRNA extracted from THP-1 cells was detected by RT-PCR and the protein was detected by FACS.The dual-luciferase reporter assay system was employed to detect the activity of ILT4 promoter with or without IL-10.The results showed that the activity of pGL3-ILTP was significantly increased and was more than ten times that of pGL3-Basic cells.After culture with IL-10 for 12 h, the expression of ILT4 protein and its mean fluorescence intensity (MFI) were increased.Moreover, the mRNA was remarkably higher than that of the control group.Dual-luciferase reporter assay revealed that ILT4 promoter was much more activated after being treated with IL-10.We were led to conclude that pGL3-ILTP containing ILT4 promoter was constructed successfully.The expression of ILT4 could be up-regulated by IL-10 both at the transcriptional and translational level.Furthermore, ILT4 promoter could be much more active after addition of IL-10.This study suggests that IL-10 up-regulates ILT4 expression on monocytes via increasing ILT4 gene promoter activity, which may have implication for inducing transplantation tolerance in clinical practice.

缺锌对大鼠肺组织IFN—r及IL—4的影响

目的:探讨缺锌对大鼠肺组织γ干扰素(IFN—r)和白细胞介素4(IL—4)的影响。方法:SD大鼠24只,按体重随机分为3组,每组8只。A组为缺锌饲料组;B组为正常锌饲料组;C组为正常锌饲料配对饲养组。建立缺锌模型,利用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测肺组织匀浆中IFN—r和IL—4的含量;RT—PCR检测肺组织中IFN—r、IL—4 mRNA表达。结果:与B组相比,A组大鼠肺组织匀浆中IFN—r含量、IFN—r mRNA的表达均明显减少(P<0.05),而IL—4含量I、L—4 mRNA的表达两组无显著差异(P>0.05)。B组与C组相比所有检测结果无显著性差异。结论:大鼠缺锌时其肺组织IFN—r明显减少,而IL—4不受影响,Thl/Th2细胞比例失衡,这可能是缺锌导致呼吸道疾病增加的重要原因。

Maternal Murine Cytomegalovirus Infection during Pregnancy Up-regulates the Gene Expression of Toll-like Receptor 2 and 4 in Placenta

Increasing evidence has revealed that maternal cytomegalovirus （CMV） infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation. Meanwhile, abnormal expression of Toll-like receptor 2 （TLR2） and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies. IL-6 and IL- 10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders. To investigate whether murine CMV （MCMV） infection causes alterations in placental IL-6/10 and TLR2/4 levels, we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection. Mouse model of acute MCMV infection during pregnancy was created, and pre-pregnant MCMV infected, lipopolysaccharide （LPS）-treated and uninfected mice were used as controls. At E13.5, E 14.5 and E 18.5, placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed. The results showed that after acute MCMV infection, the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5, accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights. However, LPS 50 ktg/kg could decrease the IL-6 expression at E13.5 and E14.5. This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more pro- inflammatory cytokine IL-6. High dose of LPS stimulation （50 gg/kg） during pregnancy can lead to down-regulation of IL-6 levels in the late stage. Imbalance of IL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.

Paradoxical Roles of IL-4 in Tumor Immunity

Interleukin(IL)-4 is a crucial cytokine in tumor immunology.In the initial murine experiments,IL-4 exhibited potent anti-tumor ability.Tumors genetically modified to produce IL-4 were rejected,while parental tumors grew progressively.Mice rejected IL-4-producing tumors got long-lasting anti-tumor immunity.The comparative study showed that IL-4 induced the most effective immune response among several cytokines in both prophylactic and therapeutic models.All of these indicate IL-4 has strong potential as a tumor therapy agent.However,contrary evidence indeed exists,and is becoming more and more abundant which shows IL-4 is a tumor-promoting molecule.IL-4 amounts are usually elevated in human cancer patients.IL-4 knockout mice are more resistant to tumor challenge than IL-4 competent mice.Furthermore,tumor cells of various histological origins often express increased levels of IL-4 receptor in comparison to their normal counterparts.By carefully examining presently available data,we found the effects of IL-4 in tumor immunity are closely related to its sources,expressing time and dose,as well as the molecular and cellular environments.In this mini-review,we concentrate on illustrating the paradoxical roles and underlying mechanisms of IL-4 in tumor immunity and try to understand how one molecule has opposite effects.

复方利多卡因乳膏对小鼠接触性皮炎模型的治疗作用及免疫学机制探讨

目的观察复方利多卡因乳膏对接触性皮炎模型小鼠的治疗作用并探讨其免疫学机制。方法采用二硝基氯苯(DNCB)诱导小鼠接触性皮炎模型,均刺激4次。并将其随机分为模型对照组、复方利多卡因乳膏低、中及高剂量组[0.032,0.064,0.096g/(d·cm2)]和阳性药物[哈西奈德乳膏0.096g/(d·cm2)]对照组,每组12只;并另选择12只未致敏小鼠作为正常对照组。各用药组分别外涂药物于小鼠右耳的正和反两面,连用15d,正常对照组和模型对照组分别予空白基质外涂。用肉眼观察小鼠右耳结痂情况、测厚仪测量右耳中部厚度、电子天平称量左右耳片重量、ELISA法测定血清IL-2,IL-4,IL-12,IL-18及IFN-r水平。结果复方利多卡因乳膏低、中及高剂量组和哈西奈德乳膏组耳结痂发生率(41.67%、25.00%、8.33%和8.33%)、第4次激发后耳肿胀度(0.352±0.049,0.322±0.054,0.305±0.059和0.301±0.058)、左右耳重量差(5.678±3.642,3.092±1.937,2.106±1.034和14.731±2.857)均小于模型对照组(91.67%,0.404±0.077,8.642±2.369);另外,其血清IL-2、IL-12和IFN-r水平均高于模型对照组;血清IL-4和IL-18水平均低于模型对照组。以上均呈现良好的量-效依赖关系,差异均有统计学意义(P均<0.05)。结论复方利多卡因乳膏对接触性皮炎模型小鼠有良好的治疗作用,其治疗机制可能与调节血清Th1和Th2平衡有关。

肾病综合征患儿T细胞亚群与激素敏感关系的研究

目的:探讨原发性肾病综合征(INS)患儿外周血T细胞亚群与激素(GC)治疗效应的关系。方法:按激素疗效的不同将31例INS患儿分为激素敏感组(17例)及激素耐药组(14例),及20例对照组均于治疗前抽取静脉血分离单个核细胞,加入植物血凝素刺激其生长、传代。48h～72h时后取其上清液,用酶联免疫吸附双抗夹心法(ELISA)检测IL4、IFNr。结果:INS中激素敏感组体外PBMCs经PHA刺激产生的IL4水平(195.70±36.61)明显高于激素耐药组(121.17±43.81)及对照组(37.20±12.89)(P<0.01);INS患儿的IFNγ水平明显高于对照组(194.15±30.53),激素组(606.17±201.03)及激素组(485.64±198.33)之间差异无显著性P>0.05。结论:NS患儿外周血Th2细胞亚群表达升高可能是GC治疗敏感的原因之一。

清热祛湿法抗流感病毒的实验研究

目的 观察清热祛湿法对流感病毒所致小鼠病毒性肺炎的作用,通过探讨清热祛湿药物的抗流感病毒免疫调节机制,为指导临床辨证治疗流感提供实验依据.方法 （1）观察清热祛湿法体外抗病毒作用及对小鼠流感病毒性肺炎的影响.（2） 用FM1株甲1型流感病毒感染小鼠.制作病毒性肺炎模型,将小鼠随机分为正常组、模型组、蒿芩清胆汤组、病毒唑对照组,分别用单标法流式细胞仪及ELISA法测定四组小鼠外周血T淋巴细胞哑群（（CD3/CD4、CD8）百分比及比值及血清IL-4、IL-18、IFN-γ的含量.结果 清热祛湿法在体外对流感病毒FM1株无明显的抑制作用,但对小鼠流感病毒性肺炎均有抑制作用,与模型对照组比较,差异有显著性意义（P〈0.05）,与病毒唑组比较,差异无显著性意义（P〉005）蒿芩清胆汤对小鼠感染流感病毒FM1后血中的CD3＋CD4＋百分比和CD3＋CD4＋/CD3＋CD8＋比值下降有一定的抑制作用并且能够降低模型小鼠血清TIL-18及IFN-r的值.结论 清热祛湿药物对流感病毒具有抑制作用,但不是直接杀死流感病毒,而是一方面通过调整T细胞亚群的百分率或CD4＋CD4＋/CD4＋CD8＋比值,另一方面通过降低IFN-r、IL-18表达水平,对流感病毒感染引起的细胞免疫功能降低有一定的抑制作用,从而减少异常的细胞免疫反应,调节和加强体液免疫功能,有利于损伤组织的修复.

More stories on Th17 cells

For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. The Thl/Th2 paradigm implied the existence of two different, mutu- ally regulated, CD4＋ T helper subsets： Thl cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particu- larly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4＋ T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Thl or Th2 cells. The Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Thl, Th2 and Th17 effector cells but there is also a di- chotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-β or TGF-β plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.

Evaluation of the adjuvanticity of artemisinin with soluble Leishmania major antigens in BALB/c mice

Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Gu fin （BCG） vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. Conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.

低浓度苯对大鼠部分血液指标的影响

为探讨低浓度苯对大鼠血常规、某些生化指标以及T淋巴细胞亚群和r -干扰素 (IFN -r)、白细胞介素 - 4(IL - 4)等指标的影响 ,以及探讨这些指标对苯的敏感性。Wistar大鼠随机分为染毒 1月组、 2月组、 3月组 ,每组分别为 2 0mg/m3、 3 0mg/m3、 40mg/m3染毒小组和一个对照组 ,每组 40只 ,雌雄各半。采用静式吸入染毒法 ,每天 1次 ,每次 2小时 ,每周连染 5天 ,持续 1～ 3个月。染苯早期 ,苯毒刺激T细胞活化 ,使IFN -r、IL - 4增加 ,之后 ,IFN -r抑制了T细胞的增殖 ,出现CD+ 3、CD+ 4减少 ,使机体细胞免疫功能减弱。与对照组比较 ,LY %与GR %减少 ,WBC在正常范围 ;红细胞系统与 6项生化指标无明显变化。

Macrophage-derived IL-1α promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity

The metabolic intermediate of acetaminophen(APAP)can cause severe hepatocyte necrosis,which triggers aberrant immune activation of liver non-parenchymal cells(NPC).Overzealous hepatic inflammation determines the morbidity and mortality of APAP-induced liver injury(AILI).Interleukin-1 receptor(IL-1R)signaling has been shown to play a critical role in various inflammatory conditions,but its precise role and underlying mechanism in AILI remain debatable.Herein,we show that NLRP3 inflammasome activation of IL-1βis dispensable to AILI,whereas IL-1α,the other ligand of IL-1R1,accounts for hepatic injury by a lethal dose of APAP.Furthermore,Kupffer cells function as a major source of activated IL-1αin the liver,which is activated by damaged hepatocytes through TLR4/MyD88 signaling.Finally,IL-1αis able to chemoattract and activate CD11b^(+)Gr-1^(+) myeloid cells,mostly neutrophils and inflammatory monocytes,to amplify deteriorated inflammation in the lesion.Therefore,this work identifies that MyD88-dependent activation of IL-1αin Kupffer cells plays a central role in the immunopathogenesis of AILI and implicates that IL-1αis a promising therapeutic target for AILI treatment.