细胞因子IL6、IL8及IL-10与变应性鼻炎的关系研究

目的探讨白细胞介素-6、8、10与变应性鼻炎（allergicrhinitis,AR）发病的相关性,为指导临床治疗提供实验依据。方法应用酶联免疫吸附测定（enzymelinkedimmu—nosorbentassay,ELISA）方法检测35例正常健康对照组以及60例变应性鼻炎患者脱敏治疗前后血清标本中IL-6、IL-8、IL-10的表达水平,并应用SPSSl3．0软件分析治疗前后各指标的表达差异,以及三者之间的相关性。结果IL-6、IL-8在AR患者血清中高表达,与健康对照组相比差异具有显著性（t=15．213,P〈0．01;t=12．231,P〈0．01）,脱敏治疗后表达均下降,治疗前后差异具有统计学意义（t=21．995,P〈0．01;t=19．766,P〈0．01）;IL-10在患者血清中表达低于对照组（t=7．446,P〈0．01）,脱敏治疗后其表达上升,与治疗前相比差异显著（t=10．228,P〈0．01）;IL-6、IL-8在AR患者中的表达呈正相关（r=0．523。P〈0．01）,而二者与IL-10的表达呈负相关（r=-0．482,P〈0．01）。结论IL-6、IL-8及IL-10与变应性鼻炎发病过程密切相关,相应的细胞因子或拮抗剂将可能成为候选的治疗药物。     

TNF-α、IL-10在变应性鼻炎中的作用研究

目的 通过检测变应性鼻炎(AR)患者血清TNF-α、IL-10在治疗前后的表达变化,探讨二者在变应性鼻炎中的作用.方法 收集33例正常健康对照组以及48例变应性鼻炎患者行脱敏治疗前后的血清标本,应用双抗体夹心ELISA方法测定血清中TNF-α、IL-10的表达水平,SPSS12.0软件进行统 计学分析.结果 TNF-α在AR患者血清中高表达,与对照组相比差异具有统计学意义(P =0.0028),脱敏治疗后其表达下降,治疗前后相比有统计学差异(P =0.0032);IL-10在患者血清中表达低于对照组,差异具有统计学意义(P=0.018),脱敏治疗后其表达上升,与治疗前相比差异有统计学意义(P=0.024);TNF-α、IL-10在AR患者中的表达呈负相关(r=-0.413,P＜0.05).结论 TNF-α和IL-10在变应性鼻炎发病过程中可能起到重要作用.     

尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10检测的临床意义

目的:探讨了尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10水平变化及意义.方法:应用RIA和ELISA对40例尖锐湿疣患者进行了血清TNF-α、IL-6、IL-8、IL-10水平检测并与35名正常健康人作比较.结果:在治疗前尖锐湿疣患者血清IL-6及IL-8低于正常对照组.TNF-α、IL-10水平均非常显著地高于正常对照组(P＜0.01),经治疗3个月后与正常对照组比较仍有显著性差异(P＜0.05).结论:检测尖锐湿疣患者血清TNF-α、IL-6、IL-8、IL-10水平的变化对疾病的治疗、预后观察有重要的临床价值.     

Graves病131I治疗后一年内缓解和早发甲减患者血清IL-18和TRAb的变化分析

探讨131I治疗后一年内GD患者甲减的免疫功能状态的改变.采用CLIA、IRMA和EIA方法,监测41例GD患者131I治疗前后血清白细胞介素-18(IL-18)、促甲状腺素受体抗体(TRAb)、TPOAb的含量和甲状腺重量(TDW)变化.41例GD患者分为甲减组13例和缓解组28例.结果表明治疗前两组GD患者血清IL-18和TRAb水平明显升高,与对照组比较均有显著性差异(P＜0.01,P(0.05),两组间比较,血清FT3、FT4、sTSH、TDW和131I剂量均无显著性差异(P＞0.05).治疗后两组血清IL-18明显下降,甲减组血清sTSH升高明显(P＜0.01),而缓解组TDW明显减少(P＜0.05).两组患者治疗后的TRAb水平仍然较高(P＜0.05).IL-18与FT3、FT4和TDW呈正相关(r=0.372,P＜0.01;r=0.312,P(0.01;r=0.371,P＜0.01),与sTSH呈负相关(r=-0.224,P＜0.01).甲减组TPOAb升高的病例治疗前为4/13,治疗后为6/13;缓解组治疗前为10/28,治疗后为12/28.131I治疗后6～12个月内辐射对患者免疫系统的调控产生的直接影响较小,血IL-18含量变化如结合TRAb、TPOAb指标了解甲状腺Th1/Th2型免疫应答状态,对疗效观察和预后判断有阶段性指导作用.     

支气管哮喘患者血清IL-10与IgE水平变化的研究

分别用ELISA、IRMA法对50例支气管哮喘急性发作患者和48名对照者血清IL-10、IgE进行测定.结果是: 支气管哮喘患者IL-10含量明显低于对照组(P＜0.01), 而IgE含量则明显高于对照组(P＜0.01), 两者之间呈明显负相关(r=-0.18,P＜0.01).结论是: 支气管哮喘患者IL-10不足、IgE水平增高可能成为其发病的重要原因之一.     

肝硬化患者血清IGF-I和IL-6、IL-8检测的临床意义

目的 探讨肝硬化患者血清IGF-Ⅰ和IL-6、IL-8水平的变化及临床意义.方法 应用放射免疫分析法,对33例肝硬化患者进行血清IL-6、IL-8和IGF-1含量的测定,并与同期收集的32名正常健康人作比较.结果 肝硬化患者血清IGF-Ⅰ水平非常显著地低于正常人组（P＜0.01）,而血清IL-6、IL-8水平非常显著地高于正常人组（P＜0.01）.且血清IGF-Ⅰ水平和IL-6、IL-8水平呈显著负相关（r=-0.4025、-0.5236,P＜0.01）.结论 检测肝硬化患者血清IGF-Ⅰ和IL-6、IL-8水平的变化,对该病的诊断、指导肝硬化的治疗及观察疗效均有重要的临床价值.     

肝硬化患者血清AFP、TNF-α、IL-6、IL-10检测的临床意义

目的:探讨了肝硬化患者血清中AFP、TNF-α、IL-6、IL-10水平及意义.方法:分别应用RIA和ELISA对63例肝硬化患者进行了血清AFP、TNF-α、IL-6、IL-10水平测定,并与35例正常健康人做比较.结果:肝硬化患者血清AFP、TNF-α、IL-6、IL-10水平均非常显著的高于正常人组(P＜0.01),且AFP水平与TNF-α、IL-6、IL-10水平呈明显的正相关(r=0.5988、0.6138、0.6284,P＜0.01).结论:AFP、TNF-α、IL-6、IL-10在肝硬化的防病机理中有一定的临床价值.     

脑梗死患者治疗前后血清IL-2、IL-6和VEGF检测的临床意义

目的:探讨32名脑梗死患者治疗前后血清IL-2、IL-6和VEGF水平的变化及意义.方法:分别应用放射免疫分析和ELISA对32例脑梗死患者进行了血清IL-2、IL-6和VEGF水平的测定,并与35名正常健康人做比较.结果:在治疗前血清IL-6、VEGF水平非常显著地高于正常人组(P＜0.01),而IL-2水平则显著地低于正常人组(P＜0.01).经治疗后3个月与正常人比较,仍有显著差异(P＜0.05).结论:脑梗死的发生、发展与血清IL-2、IL-6和VEGF水平密切相关.     

急性结膜炎患者治疗前后血清hs-CRP、IL-6、IL-10、IL-18检测的临床意义

目的:探讨了急性结膜炎患者治疗前后血清hs-CRP、IL-6、IL-10、IL-18水平的变化及意义.方法:分别应用放免法、免疫比浊法和酶联法对38例急性结膜炎患者进行了血清hs-CRP、IL-6、IL-10和IL-18水平检测,并与35名正常健康人作比较.结果:急性结膜炎患者在治疗前血清hs-CRP、IL-6、IL-10和IL-18水平均非常显著地高于正常人(P＜0.01),经2周的抗炎治疗后则与正常人比较无显著性差异(P＞0.05).结论:检测急性结膜炎患者血清hs-CRP、IL-6、IL-10和IL-18水平的变化对临床观察预后有重要的临床价值.     

新疆维、汉人群变应性鼻炎患者血清IL-4和IFN-γ水平及其与鼻粘膜嗜酸性粒细胞浸润的相关性

目的:探讨新疆维、汉人群变应性鼻炎(Allergic rhinitis,AR)患者血清白细胞介素4(Interleukin-4,IL-4)和干扰素γ(Interferon gamma,IFN-γ)水平与鼻粘膜嗜酸性粒细胞(Eosionphils,EOS)浸润的相关性。方法:采用酶联免疫吸附法(Enzyme-linked immunosorbnent assay,ELISA)测定59例维吾尔族AR患者、50例汉族AR患者外周血清IL-4和IFN-γ水平,高倍显微镜下观察病理涂片并计数AR患者鼻粘膜EOS计数。结果:维、汉人群AR患者血清IL-4和IFN-γ水平均无显著差异(t值分别为1.304和1.408,P均>0.05);维、汉人群AR患者IL-4水平与鼻粘膜嗜酸性粒细胞计数均呈正相关(r分别为0.828和0.691,P均<0.01),IFN-γ水平与鼻粘膜EOS计数均呈负相关(r分别为-0.712和-0.764,P均<0.01)。结论:维、汉人群AR患者的血清IL-4和IFN-γ水平均无显著差异,AR患者鼻粘膜EOS增多与血清IL-4分泌过多而IFN-γ分泌受抑制有关。     

高浓度rIL-2对休止PBL IL-2R_α口的诱导作用

本文利用~(125)I标记的抗IL-2R_α单克隆抗体,探讨了rIL-2对IL-2R_α的调节作用。结果显示,rIL-2除可增加已活化的T淋巴细胞IL-2R_α表达外,高浓度情况下可直接诱导休止的PBL IL-2_α表达,表达高峰在第5天以后,B_(maxc)为7200位点/每细胞。高浓度IL-2诱导的PBL ~3H-TdR和~3H-UR掺入水平与IL-2_α表达量呈正相关,表明高浓度rIL-2通过诱导IL-2_α表达而引起休止细胞的增殖。     

Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles"

Purpose

We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children.

Methods

This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children.

Results

The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children''s genotypes, we observed interactive effects on children''s IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant.

Conclusion

Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children''s genetic effects. These effects differ in "Western or Eastern" environments.     

新生儿全身炎症反应综合征与IL-10基因多态性的相关性研究

目的探讨IL-10基因启动子区1082位点基因型及等位基因与新生儿全身炎症反应综合征(SIRS)的关系。方法采用ELISA法检测血清IL-10水平及限制片断长度多态分析-聚合酶链反应方法(RFLP/PCR)对54例全身炎症反应综合征新生儿和40例随机挑选健康体检的新生儿的IL-10的基因启动子区1082位点等位基因进行分析,计算该位点的基因分布频率和相对危险度OR值;并进行卡方检验,筛选有意义基因型。结果(1)SIRS组血清IL-10水平显著升高,与对照组比较差异显著。(2)SIRS组患儿IL-10 1082位点GG型分布频率为61.1%,AA分布频率为5.6%,GA分布频率为33.3%,以上三个基因型在疾病组与正常组之间进行卡方检验,χ2值分别为7.53,1.30,6.00,GG型与正常对照组比较均有显著性差异(P<0.01)。AA型与正常对照组比较亦有显著性差异(P<0.05)。疾病组G等位基因的分布频率为77.8%;A等位基因的分布频率为22.2%;疾病组与正常组之间进行逐个基因型的比较,以相对危险度0R值计算,计算结果GG的0R值为3.26;AA的0R值为0.20;GA的0R值为0.61。结论IL-10的基因启动子区1082位点GG是中国北方汉族新生儿SIRS的易感基因;而AA为抗感基因。通过对IL-10基因启动子区1082位点的基因多态性的搜索,发现IL-10基因启动子区1082位点的基因型对新生儿SIRS的发生、发展、诊断、预后、预测有重要意义。     

过敏性紫癜患儿血清sIL-2R、IL-6、IL-8 及凝血功能的变化

目的　探讨过敏性紫癜 (HSP)患儿血清可溶性白介素 2受体 (sIL - 2R)、白介素 6 (IL - 6 )、白介素 8(IL - 8)及部分凝血活酶时间 (APTT)、凝血酶时间 (TT)、D -D二聚体在发病过程中的变化。方法　应用化学发光法检测sIL - 2R、IL -6、IL - 8水平 ,用SymexCA - 15 0 0全自动血凝分析仪测定APTT、TT及D -D二聚体。结果　HSP患儿急性期血清sIL - 2R、IL- 6、IL - 8水平明显高于正常 (P <0 0 5 ) ,3个月后恢复至正常对照组水平 (P >0 0 5 )。早期血液呈高凝状态 ,APTT、TT缩短 ,伴继发性纤溶 ,D -D二聚体增高 ,且混合型增高更显著。结论　动态检测HSP患儿血清sIL - 2R、IL - 6、IL - 8及APTT、TT、D -D二聚体的变化 ,为临床判断病情 ,估计预后及抗凝治疗提供理论依据。     

红斑型银屑病患者他克莫司治疗前后IL-17 A、 IL-22和IL-6的变化分析

目的：旨在评估外用他克莫司（tacrolimus）软膏（0．03％）治疗银屑病患者前后血清中关键的细胞因子水平以及和临床指征的相关性。方法收集性别和年龄匹配的45名用他克莫司软膏（0．03％）治疗前和治疗一个月后银屑病患者和30名正常健康志愿者的血清样品后,用酶联免疫吸附实验（ ELISA）检测这些样本的细胞因子[（interleukin, IL） IL?17A、 IL?6、 IL?22和IL?21]水平,用实时定量RT?PCR分析这些因子的表达水平。用银屑病皮损面积和严重指数（ psoriasis area and severity index, PASI）评估银屑病患者治疗前的得分。结果银屑病患者治疗前血清中IL?17A, IL?22和IL?6浓度显著高于对照组,皮损组织中的mRNA水平也高于正常对照组（ P＜0．01）,虽然他克莫司治疗后血清中这些细胞因子显著下降（P＜0．01）,但仍高于正常人群对照组（P＜0．05）。银屑病患者治疗前后血清中IL?21和治疗前皮损中IL?21 mRNA与对照比较无显著性差异。本研究中发现IL?17A和IL?22细胞因子浓度与PASI得分有正相关,但与年龄无显著相关性。结论他克莫司治疗能减轻银屑病的症状,其机制可能与血清中IL?17A、 IL?22和IL?6的下降相关。     

磁性免疫微球的合成及其在基因重组IL-2纯化中的应用

本文在合成Fe3O4磁性材料的基础上,制备出agarose－Fe3O4磁性动体激球,并通过优化合成条件,建立了一套制备磁性微球的合成方法。将其与抗rhIL-2单克隆抗体（mAb）连接制备的免疫磁性极球一步纯化rhIL-2后,经SDS-PAGE、光密度扫描和CTLL细胞活性测定表明,纯度为93％,活性回收率为80％,比活性为2．0x109IU／g蛋白质。结果说明磁性免疫微球不失为一种简单、快速分高蛋白质的方法。     

Association of the interleukin (IL)-16 gene polymorphisms with Graves' disease

Interleukin (IL)-16 was one of the cytokines with the function of T helper cell recruitment, whose expression in the thyrocyte and orbital fibroblast of Graves' disease (GD) patients was increased. Recently association of IL-16 gene polymorphisms with autoimmune diseases had been reported. However, there was little known about the impact of IL-16 gene polymorphisms on GD. In this study, we performed a case-control association study of three tagSNPs (rs4778889–rs1131445–rs4778641) within the IL-16 gene on 258 patients with GD and 208 healthy subjects in the Chinese population. Our data showed that common IL-16 variants were associated with GD (P = 0.013–0.0186) and Graves' disease associated ophthalmopathy (GO) (P = 0.0033–0.041). A novel protective haplotype containing the three tagSNPs (C–T–C) was observed in association with GO (P = 0.013). In conclusion, IL-16 gene was significantly associated with susceptibility to Graves' disease and Graves' disease associated ophthalmopathy in the Chinese population.     

The role of IL 23 in the treatment of psoriasis

Introduction: The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade.

Areas covered: Relevant references regarding the role of the IL-23/IL-17 pathway in the pathogenesis of psoriasis/psoriatic arthritis and clinical trials with IL-23p40 and IL-23p19 blocking agents were obtained through a literature search in MEDLINE/Pubmed for articles published until November 2016. Moreover, ongoing registered clinical trials (RCTs) of moderate-to-severe psoriasis and psoriatic arthritis were searched through clinicaltrials.gov website, and a manual search was made for pertinent communications at the 2016 American Academy of Dermatology and European Academy of Dermatology and Venereology meetings.

Expert commentary: There are potential advantages in selective blockade of the IL23-specific p19 subunit with respect to distal blockade of IL-17A or its receptor. Acting upstream in the IL-23/IL-17 cytokine pathway is likely to reduce the expression of multiple pro-inflammatory cytokines acting on keratinocytes -including IL-17F, IL-21 and IL-22-, in addition to IL-17A. On the other hand, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering or worsening of inflammatory bowel disease.

Specific IL-23p19 blockade with high-affinity monoclonal antibodies seems to be able to induce long-term remissions of the activity in psoriasis and might eventually represent a paradigm change in the treatment of psoriasis. The results of phase III and comparative head-to-head trials with these agents are eagerly awaited.     

The IL1A genotype is associated with nasal polyposis in asthmatic adults

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease often found coexisting with asthma. As this disorder tends to cluster in families, a genetic predisposition has been suggested. Interleukin-1 (IL-1) has been proposed to play a role in the pathogenesis of NP. METHODS: We analysed the single G-to-T base exchange polymorphism in exon 5 at +4845 of the gene encoding IL-1alpha (IL1A) and the C-to-T base exchange polymorphism at -511 of the gene encoding IL-1beta (IL1B) in a population-based sample of adult asthma patients (n = 245). The data were assessed for correlation with data on history of NP and other phenotype-related characteristics. RESULTS: The prevalence of NP in our study group was 14.3%. The distribution of the IL1A genotype differed significantly between asthmatics with and without NP (P = 0.005). The risk of NP was markedly increased in allele G homozygous subjects (OR = 2.73; 95%CI = 1.40-5.32). In the case of IL1B we found no significant associations. Asthmatics with NP had more symptoms than others, but lung function and blood eosinophil counts were similar. CONCLUSIONS: Our study demonstrates an association of IL1A with NP inasthmatic patients and addresses the role of IL-1alpha as an inflammatory modulator in the pathogenesis of this disease.