狼疮性肾炎患者Th1、Th17及Th22细胞亚群的变化及临床意义

目的研究狼疮性肾炎（LN）患者外周血辅助性T细胞1（Th1）、辅助性T细胞17（Th17）和辅助性T细胞22（Th22）及其细胞因子干扰素一1（IFN一1）、白细胞介素17（IL－17）和白细胞介素22（1L－17）的表达情况及其临床意义。方法流式细胞术检测20例LN患者组和20例健康对照组外周血中Th1、Th17和Th22细胞比例;酶联免疫吸附试验（ELISA）检测血清中相关细胞因子IFN－1、IL－17及IL－22水平,并进行相关性分析。结果相较健康对照组,LN组外周血中Th17细胞比例增高（P〈0．05）,Th22细胞比例减低（P〈0．05）,而Th1细胞比例无差异（P〉0．05）;LN组血清中IL－17水平增高（P〈0．05）,IL－22水平减低（P〈0．05）,而IFN－γ水平无差异（P〈0．05）;Th17细胞比例分别与血清IL－17、系统性红斑狼疮疾病活动指数（SLEDAI）呈正相关（r=0．721,P〈0．05;r=0．225,P〈0．05）,而Th22细胞比例与血清IL－22水平呈正相关（r=0．489,P〈0．05）与SLEDAI评分无相关性（r=0．241,P〉0．05）。结论Th17及Th22在LN患者中异常表达可能导致患者自身免疫功能紊乱,促进疾病病理损伤。     

卡泊三醇外涂软膏联合激光光疗治疗银屑病对患者血清 TNF－α、IL－17、IL－23水平的影响

目的：分析卡泊三醇外涂软膏联合激光光疗治疗银屑病的疗效及对患者血清肿瘤坏死因子－α（TNF－α）、白细胞介素－17（IL－17）、白细胞介素－23（IL－23）水平的影响。方法将208例银屑病患者随机分为研究组及对照组各104例。对照组采用激光治疗,研究组采用卡泊三醇外涂软膏联合激光光疗治疗。比较2组的临床疗效及患者血清TNF－α、IL－17、IL－23水平的变化。结果经3个月的治疗,研究组治疗的总有效率为97．1％高于对照组的59．6％,差异有统计学意义（ P＜0．05）。经3个月的治疗,2组患者的血清TNF－α、IL－17、IL－23水平均低于治疗前,且研究组低于对照组,差异均有统计学意义（P＜0．05）。结论卡泊三醇外涂软膏联合激光光疗治疗银屑病,能有效降低患者血清TNF－α、IL－17、IL－23水平,临床疗效显著,值得推广应用。     

深静脉血栓形成患者辅助T细胞亚群17的变化及意义

目的探讨深静脉血栓形成患者外周血辅助T细胞亚群17（Th17）及其细胞因子白介素17（IL－17）的变化及临床意义。方法选取82例深静脉血栓形成患者,分为急性期29例,亚急性期24例,慢性期29例．另选20例同期门诊体检者中的健康者作为对照组。采用流式细胞术检测外周血Th17细胞的百分率,酶联免疫吸附测定法（ELISA）检测血浆中IL—17的表达水平。结果深静脉血栓形成患者组外周血Th17细胞百分率及IL－17的表达水平均高于健康对照组,差异有统计学意义（P〈0．05）,不同分期患者组间Th17细胞百分率及IL－17的表达水平比较,差异无统计学意义。结论深静脉血栓形成患者外周血Th17细胞活性增高。Th17细胞激活可能与深静脉血栓形成发病及病程进展密切相关。     

肾病综合征患儿白细胞介素10在外周血单个核细胞中基因表达的研究

目的：探讨白细胞介素10（IL－10）在小儿原发性肾综合征（INS）中的变化。方法：应用逆转录－多聚酶链反应（RT－PCR）及ELISA法分别检测了30例健康儿童和52例原发性肾病综合征患儿急性期及缓解期外周血单个核细胞（PBMC）在植物血凝素（PHC）刺激下IL－10mRNA和蛋白水平的变化。结果：（1）原发性肾病综合征（单纯性及肾炎性）患儿急性期IL－10mRNA与蛋白水平较正常对照组显著升高（P分别＜0．05EY 0．01）；而缓解期与正常对照组相比较无显著差异（P均＞0．05）。（2）肾炎性肾病急性期IL－10mRNA、蛋白水平均显著高于单纯性肾病综合征（P均＜0．01）。结论：原发性肾病综合征患儿存在Th1/Th2细胞免疫功能的失衡，IL－10在其发病中可能具有一定的保护作用。外周血单个核细胞IL－10水平可作为观察病情活动状态、判断临床类型的一个免疫学指标。     

荨麻疹患者外周血单个核细胞产生IL－4、IL－10及IFNγ的水平及意义

为了解荨麻疹患外周血单个核细胞（PMBC）产生IL－4、IL－10及IFNγ的水平,有用双抗体夹心ELISA法测定了23例荨麻疹患PBMC产生这3种细胞因子的水平。结果表明,IL－4水平明显高于正常人（P＜0．01）,而IL－10及IFNγ水平与正常人差异无显意义（P＞0．05）。IL－4由Th1细胞分泌,为B细胞增殖活化及IgE产生必需,其异常分泌导致IgE过量产生,在I型变态反应荨麻疹发病中起一定作用。     

中西药物疗法配合紫外线光疗治疗白癜风对患者血清 IL－17、IFN－γ及 Hcy水平的影响

目的：探讨联合中西药物疗法及紫外线光疗治疗白癜风对患者白细胞介素－17（ IL－17）、肿瘤坏死因子－γ（ IFN－γ）及同型半胱氨酸（ Hcy）的影响。方法将240例白癜风患者随机分为研究组和对照组各120例。对照组接受中西药物疗法治疗,研究组接受联合紫外线光疗及中西药物疗法治疗。对比2组治疗前后IL－17、IFN－γ及Hcy含量变化情况。结果治疗前2组IL－17、IFN－γ及Hcy水平比较差异均无统计学意义（ P＞0．05）。治疗后2组IL－17、IFN－γ及Hcy水平均低于治疗前,且研究组低于对照组,差异均有统计学意义（P＜0．05）。结论中西药物及紫外线光疗联合疗法可有效地降低白癜风患者IL－17、IFN－γ及Hcy含量。     

宫颈癌中单核细胞对Th17细胞分化的影响

目的 检测宫颈癌病人外周血中Th17细胞的比例及相关细胞因子白细胞介素（IL）-1β、IL-6的表达水平,探讨宫颈癌外周血中单核细胞对Th17细胞分化的影响及机制。方法 2019年6月至2020年12月在潍坊市人民医院妇科收治的宫颈癌病人（宫颈癌组）39例,对照组（30例）为健康志愿者及因良性疾病在潍坊市人民医院妇科就诊的病人,流式细胞仪检测宫颈癌组、对照组外周血中Th17细胞的比例;实时荧光定量逆转录聚合酶链反应（qRT-PCR）检测宫颈癌病人、对照组外周血中IL-1β、IL-6的表达水平;分离健康志愿者外周血中的初始CD4+T细胞,分别与对照组、宫颈癌组外周血中分离出的单核细胞进行共培养,并分别加入anti-IL-1β、anti-IL-6中和抗体,流式细胞仪检测Th17细胞的比例。结果 宫颈癌组外周血中,Th17细胞比例（3.5±1.4）%、IL-1β 0.457(0.078,1.193)、IL-6 0.094(0.043,0.272)的表达水平明显高于对照组（2.3±1.6）%、0.279(0.017,0.686)、0.038(0.019,0.112)。初始CD4+T细胞与宫颈癌...     

纳洛酮分别联合更昔洛韦与病毒唑对病毒性脑炎患儿血清 IL－1、TNF－α水平的影响比较

目的：观察纳洛酮分别联合更昔洛韦与病毒唑治疗小儿病毒性脑炎的疗效及对血清白细胞介素－1（IL－1）、肿瘤坏死因子－α（TNF－α）水平的影响。方法将病毒性脑炎患儿120例随机分为试验组和对照组各60例,给予所有患儿常规治疗和护理,试验组给予纳洛酮联合更昔洛韦治疗,对照组给予纳洛酮联合病毒唑治疗,治疗1周后评价2组患儿治疗效果,并于治疗前后抽取2组患儿静脉血,检测并评价血清IL－1、TNF－α水平变化。结果试验组患儿治疗总有效率为93．33％高于对照组的76．67％;治疗后2组患儿血清IL－1、TNF－α水平均呈下降趋势,但试验组降幅大于对照组,差异均有统计学意义（ P＜0．05）。结论纳洛酮联合更昔洛韦治疗小儿病毒性脑炎的治疗效果优于纳洛酮联合病毒唑治疗,且对血清IL－1、TNF－α水平下降幅度的影响更为显著。     

Th1／Th2／Th17 T／reg 对鉴别儿童支气管哮喘与单纯性肺炎的意义

目的：检测Th1（IFN-γ＋）、调节T细胞（CD2＋5Foxp3＋）、辅助T 细胞17（Th17）及细胞因子IL-2、IL -4、IL-17和IL-21在儿童支气管哮喘以及肺炎患儿外周血中的表达,探讨其在儿童支气管哮喘发病中的作用以及与肺炎鉴别的意义。方法收集哮喘患儿32例,肺炎患儿37例作为研究对象,选取同期体检的22例健康儿童为对照组。分离外周血单个核细胞,采用流式细胞术检测CD 4＋IFN-γ＋、CD 4＋CD 2＋5Foxp 3＋、CD4＋Th17＋细胞百分率。采用酶联免疫吸咐（ ELISA）法检测3组IL-2、IL-4、IL-17、IL-21表达水平。结果哮喘组患儿外周血CD4＋CD2＋5 Foxp3＋细胞占CD4＋T细胞的比率明显低于肺炎组及对照组;哮喘组患儿者外周血CD4＋IFN-γ＋细胞比例明显低于肺炎组和对照组;哮喘组患儿者外周血CD4＋Th17＋细胞所占比例高于肺炎组及对照组,差异均有统计学意义（ P ＜0*．05）。哮喘组患儿外周血IL-2的浓度明显低于对照组（ P ＜00．5）,肺炎组患儿外周血IL-2浓度明显低于对照组（ P ＜0．05）,但与哮喘组比较差异无统计学意义（ P ＞0．05）。哮喘组患儿外周血 IL4-、IL-17和IL-21的浓度明显低于肺炎组和对照组,差异有统计学意义（ P ＜0．05）。结论 Th1／T2h ／Th17／Treg功能失调参与了儿童支气管哮喘的发病机制,临床上可以通过检测Th1／Th2／Th17／Treg相关细胞因子的变化评估儿童支气管哮喘病情并辅助与肺炎的鉴别。     

孟鲁司特对哮喘患儿外周血Th1/Th2平衡的调控作用及肺功能的影响

目的观察孟鲁司特对哮喘患儿外周血Th1／Th2平衡的调控作用及肺功能的影响。方法选择80倒哮喘急性发作期惠儿,随机均分为两组。治疗组40例在对照组40例常规吸入激素治疗的基础上,加用孟鲁司特钠片5mg／d,1次／d,睡前口服,连用3月。两组患儿均于治疗前和治疗3月后检测外周血白细胞介素4（IL-4）、干扰素-γ（IFN-γ）和免疫球蛋白E（IgE）水平及肺功能的变化。结果两组患儿治疗后外周血IL-4和IgE水平明显下降,IFN-γ水平明显上升（P〈0．05或P〈0．01）,肺功能指标均明显改善（P〈0．05）,且治疗组较对照组变化更明显（P〈0．05）,改善程度更高（P〈0．05）。结论孟鲁司特治疗哮喘的临床疗效确切,能明显改善患儿的肺功能,其作用机制可能是通过纠正Th1／Th2细胞因子平衡．使免疫反应由Th2型向Th1型逆转．抑制嗜酸性细胞聚集,减少IgE分泌．     

IL-17A 及IL-17RA 在不同恶性程度胶质瘤中表达的研究

摘要： 目的 研究白细胞介素 （IL） -17A 及其受体 （IL-17RA） 在不同恶性程度胶质瘤中表达的差异。方法 收集胶质瘤患者 50 例, 按照世界卫生组织的分类系统分为Ⅰ级 12 例, Ⅱ级 18 例, Ⅲ级 13 例, Ⅳ级 7 例。取患者外周血以及胶质瘤组织, 荧光实时定量 PCR 检测 IL-17A 及 IL-17RA 的 mRNA 水平, 采用免疫组化和 Western blot 检测 IL-17A 及 IL-17RA 的蛋白表达水平。结果 免疫组化染色结果显示, 随着胶质瘤恶性程度增加, IL-17A 及其受体 IL-17RA 表达增加。外周血中, IL-17A 及其受体 IL-17RA 的 mRNA 水平随着胶质瘤恶性程度增加而上升 （F 分别为 8.96、 10.34, 均 P＜0.05）。胶质瘤组织中 IL-17A 及其受体 IL-17RA 的 mRNA 水平随着胶质瘤恶性程度增加而上升 （F 分别为 11.21、 14.11, 均 P＜0.05）。在外周血和胶质瘤组织中, IL-17A 及其受体 IL-17RA 的蛋白水平随着胶质瘤恶性程度增加也上升 （外周血 F 分别为 9.90、 11.80, 均 P＜0.05; 胶质瘤组织 F 分别为 8.15、 14.46,均 P＜ 0.05）。结论 IL-17A 及其受体 IL-17RA 的表达与胶质瘤恶性程度呈正相关性。     

桥本甲状腺炎早期外周血白介素-35水平及其临床意义

目的检测桥本甲状腺炎(hashimoto's thyroiditis,HT)患者血清白介素(interleukin,IL)-35水平并探讨其临床意义。方法选取2018年9月至2019年1月于南京中医药大学附属中西医结合医院内分泌科门诊首次就诊并诊断考虑为HT患者65例。采用酶联免疫吸附试验检测65例HT患者和20例健康对照者血清IL-35、IL-17水平并分析两者相关性及其与自身抗体相关性。结果HT患者血清IL-35水平低于健康对照者(P<0.05),而IL-17水平明显高于健康对照者(P<0.05),两者呈负相关(r=-0.512),差异有统计学意义(P<0.05);HT患者血清中IL-35水平与血清甲状腺过氧化物酶抗体(serum thyroperoxidase antibody,TPOAb)水平存在负相关(r=-0.427,P<0.05);IL-17水平与TPOAb水平存在正相关(r=0.465,P<0.05)。结论HT患者体内IL-35水平较低,IL-35水平可反映患者体内调节T细胞的数量和功能状态。患者体内IL-35与IL-17水平呈负相关,IL-35可对辅助性T细胞17起拮抗作用并抑制IL-17产生。HT患者体内IL-35水平与自身抗体呈负相关,说明IL-35对HT的发生可有保护作用,在HT早期发病中起重要作用。     

Emerging drugs for the treatment of axial spondyloarthritis

Introduction: The treatment of axial spondyloarthritis(axSpA) has been for nearly 15 years constricted to non-steroidal antirheumatic drugs and TNFα inhibitors. With the approval of secukinumab, a drug targeting the interleukin(IL)-17 axis became available. Nonetheless, an unmet need for further emerging therapeutic options remains.

Areas covered: This review summarizes the recent and ongoing clinical trials with novel drugs in axSpA. Besides secukinumab, further therapeutics directed against the IL-17A (e.g. ixekizumab) as well as the dual IL-17A and F inhibitor bimekizumab and the IL-17RA antibody brodalumab are in development. Furthermore, several drugs targeting the IL-12/-23 axis are being evaluated. Pan-JAK and JAK-1 inhibitors might offer another effective mode of action.

Expert opinion: The number of treatment options in axSpA is likely to be further extended in the coming years. Data of ongoing studies are needed to prove the efficacy of drugs directed against the IL-12/-23 axis as well as of JAK inhibition, whilst targeting the IL-17 axis was shown to be as effective as TNF inhibition by indirect comparison. There is an emerging need for trials aiming at identification of optimal treatment strategies in the scope of the treat-to-target concept in axSpA.     

Augmentation of lymphocytes activation and T cell modulation by the extracts from some Euphorbia species

Context: Euphorbia is an important Euphorbiaceae genus that is traditionally being used for various infections, inflammation, and cancer.

Objective: The present study investigated the possible in vitro immunomodulatory effect of three species of Euphorbia genus including Euphorbia microciadia Boiss, Euphorbia osyridea Boiss, and Euphorbia heteradenia Jaub. &; Sp. on lymphocyte activation and cytokine secretion.

Materials and methods: Human lymphocytes were cultured in the presence of various concentrations (0.1–200?µg/ml) of the butanol/hexane extracts of the plants in the presence or absence of phytohemmagglutinin (PHA). The activation of lymphocytes after 48?h was determined by a proliferation assay. The release of T cell cytokines was studied to determine the dominant T cell subsets involved in the immune response.

Results: All three plant extracts increased the proliferation of PHA-treated lymphocytes (maximum; 132% of control). Extract treatment of lymphocytes in the absence of PHA resulted in an increased proliferation of the cells indicating their lymphocyte mitogenic activity (maximum at 10?µg/ml E. microciadia extract; 494.5?±?42.2% of control, p?E. microciadia and E. osyridea could increase IL-4 and IL-10 secretion but not IFN-γ production showing their capacity to deviate immune response toward a Th2 pattern. Euphorbia heteradenia did not change the release of IL-4 and IFN-γ cytokines but increased IL-10 production. The three extracts stimulated lymphocytes to produce IL-17 which showed their possible effects on Th17 cells activation.

Conclusion: The studied extracts had the ability to modulate T cell responses suggesting their possible beneficial effects on immune host defense.     

Current investigational drugs in psoriasis

Introduction : The advent of biologic therapies has revolutionized the treatment of psoriasis. Increased understanding of immunogenetic pathways has allowed for the development of more selective targeted biologic therapies. Multiple new treatments are currently in development for the treatment of psoriasis. Preliminary data for many of these agents, particularly with regard to agents targeting the IL-23/Th17 pathway, are promising. Proven long-term safety, however, is an absolute necessity with newly developed drugs, and should, therefore, still be considered second-line agents to current established treatments with long-term safety data.

Areas covered : This review details the mechanisms of action of drugs currently in development or in clinical trials for the treatment of psoriasis, using clinical trial registries and associated publications. Readers will gain a comprehensive overview about the mechanism of action of emerging treatments targeting various immune pathways deeply involved in psoriasis. Pathogenesis, clinical efficacy and safety data for these treatments are discussed where available.

Expert opinion : Psoriasis remains a heavily undertreated systemic immune-mediated disease despite increased understanding of immunopathogenesis of the disease and advent of a multitude of novel therapeutic agents with potentially improved bioavailability and safety profiles. Limitations, however, remain in the realm of topical agents for treatment of mild to moderate psoriasis, which has seen little progress over the years. A concerted effort will need to be made among researchers, clinicians and patient advocacy groups to ensure new therapeutic agents are developed and gain proper exposure.     

寻常型银屑病血热证患者免疫血清学标志物的系统评价

目的：系统评价寻常型银屑病血热证患者免疫血清学标志物γ-干扰素（interferon-γ, IFN-γ）、白介素（interleukin, IL）-4、IL-17、IL-23、IL-6、α-肿瘤坏死因子（tumor necrosis factor-α, TNF-α）和IL-10水平的变化。方法：完整检索7个数据库中的近30年相关文献,纳入17篇文献,共包括768例受试者（443例寻常型银屑病血热证患者和325例健康对照者）。评价被纳入文献的研究质量并提取有效数据,然后采用随机效应模型合并受试组和对照组受试者的免疫血清学标志物水平效应量。结果：总效应量分析结果显示,受试组患者的血清IFN-γ水平（均数差24.90 pg/ml,95% CI：12.36~37.43）、IL-17水平（均数差28.92 pg/ml,95% CI：17.44~40.40）、IL-23水平（均数差310.60 pg/ml,95% CI：4.96~616.24）和TNF-α水平（均数差19.84 pg/ml,95% CI：13.80~25.87）显著高于对照组, IL-4水平（均数差-13.5 pg/ml,95% CI：-17.74~-9.26）和IL-10水平（均数差-10.33 pg/ml,95% CI：-12.03~-8.63）显著低于对照组,IL-6水平没有显著变化。结论：寻常型银屑病血热证患者的血清IFN-γ、IL-17、IL-23和TNF-α水平显著升高,而IL-4和IL-10水平显著降低。该结论尚需得到高质量、大样本量临床研究的进一步证实。     

The safety of brodalumab for the treatment of psoriasis

ABSTRACT

Introduction: Brodalumab is a newly developed targeted biologic agent for the treatment of psoriasis that blocks IL-17 receptor A.

Areas covered: This review sought to provide a detailed overview on safety of brodalumab for the treatment of psoriasis. A PubMed search was conducted for relevant literature. Here we review the efficacy and safety data from key phase II, phase III and open-label extension clinical trials, as well as systematic reviews and meta-analyses.

Expert opinion: The unique mechanism of action of brodalumab offers advantages on efficacy over other targeted treatments, with a quick onset of action and long-term maintenance of treatment response. Brodalumab has a favorable safety profile, similar to other IL-17 inhibitors. Infections, especially mucocutaneous candidiasis, must be monitored. Suicidal ideation was detected in brodalumab trials, although a causal relationship has not been revealed. Brodalumab is a highly efficacious and comparably safe therapeutic choice in patients with moderate to severe psoriasis, especially when rapid control of the disease is desired.     

Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice

Context: Our previous study showed that the interleukin-17 (IL-17) concentration in lung tissue and in bronchoalveolar lavage fluid (BALF) of rats with tobacco-smoke-induced chronic obstructive pulmonary disease (COPD) was higher than that of control group. However, whether IL-17 inhibitor could decrease the effect of tobacco smoking is not known yet.

Objectives: To investigate the significance of IL-17 antibodies (Ab) in tobacco-smoke-exposed (TSE) mice.

Materials and methods: Male C57/BL6 mice were randomly divided into three groups: TSE group, TSE + anti-IL-17 Ab group, and control group. The number of cells in BALF and the concentrations of IL-17, IL-6, IL-8 and MUC5AC in BALF and lung tissue homogenate were measured. Pulmonary function was measured by pressure sensors, and histologic analysis of the lungs was done in each group.

Results: Lung function tests in TSE + anti-IL-17 Ab group were the same compared with TSE group (P?>?0.05). The total cell count and the number of neutrophil cells in BALF were significantly higher in TSE group than the normal control group (P?<?0.01). Compared with the TSE group, the total cell count in TSE + anti-IL-17 Ab group was decreased, and the percentage of neutrophils in BALF was highly decreased (P?<?0.01). Airway inflammation was alleviated in TSE + anti-IL-17 Ab group by histologic analysis. The concentrations of IL-17 in lung tissue were significantly lower in TSE + anti-IL-17 Ab group than in TSE group (P?<?0.01). IL-17 was mainly expressed in the epithelial cells in the airways of TSE mice. The concentration of IL-6, IL-8 and MUC5AC in BALF was decreased in TSE + anti-IL-17 Ab group compared with TSE group.

Discussion and conclusions: These data support a potential role for IL-17 in airway neutrophilic inflammation in TSE mice. Anti-IL-17 decreased the number of neutrophils as well as the concentration of MUC5AC in the BALF and attenuated neutrophilic airway inflammation.     

IL-17、IL-27和FeNO与支气管哮喘儿童肺功能的相关性及其对哮喘诊断的临床价值

目的 检测哮喘患儿白细胞介素-17(IL-17)、白细胞介素-27(IL-27)和呼出气一氧化氮(FeNO)水平的变化,探讨这些指标与肺功能指标的相关性、诊断哮喘的临床价值.方法 收集2019年5月—2020年5月在漯河市中心医院儿科接受治疗的64例哮喘患儿作为哮喘组,同期体检的30例健康儿童作为对照组.记录患者入院时...