类风湿关节炎患者血清和关节液细胞因子水平的变化及临床意义

目的探讨幼年类风湿关节炎(JRA)及类风湿关节炎(RA)患者IL-6、IL-8、sIL-2R和TNF-α等细胞因子(CK)水平的变化,及其与风湿活动的传统指标血沉(ESR)和C-反应蛋白(CRP)的相关性。方法采用夹心ELISA法,对30例JRA和34例RA患者的血清中,4例JRA、7例RA、6例骨性关节炎(OA)和9例半月板损伤(MT)患者的关节液中IL-6、IL-8、sIL-2R和TNF-α的水平进行检测。结果①30例JRA、34例RA患者血清IL-6和sIL-2R的水平与对照组相差非常显著(P〈0.01);30例JRA患者血清IL-8水平与对照组比较相差显著(P〈0.05)。②JRA全身型、少关节型患者血清IL-8、sIL-2R的水平和JRA多关节型患者血清IL-6的水平与对照组相差非常显著(P〈0.01)。③4例JRA及7例RA患者关节液sIL-2R的水平和RA患者关节液的IL-6水平与对照组相差显著(P〈0.05)。④JRA患者血清IL-6和sIL-2R的水平与ESR和CRP的变化呈明显的相关关系(r值分别为0.532和0.621)。结论①IL-6、sIL-2R的水平与JRA、RA病的活动性有关,是类风湿活动性的主要指标。②sIL-2R不仅参与JRA和RA的全身病理损伤,而且是引起关节局部损伤的主要CK,IL-6也参与JRA关节局部的病理损伤,在RA关节局部损伤似乎更为重要。③IL-8主要参与JRA的全身病理损伤,对关节局部病理损伤似乎并不重要。     

类风湿关节炎湿热痹阻型患者血清和关节液IL-1、IL-6、TNF-α的表达研究

目的检测类风湿关节炎(RA)湿热痹阻型患者血清和关节液中IL-1、IL-6、TNF-α的表达水平,分析IL-1、IL-6、TNF-α与炎性活动指标ESR、CRP、DAS28之间的关系,探索细胞因子与RA发生发展的关系。方法采用ELISA法检测RA湿热痹阻型患者外周血血清90例、RA湿热痹阻型患者关节液28例、骨性关节炎患者关节液30例及健康对照组血清30例IL-1、IL-6、TNF-α的表达,并常规方法检测ESR、CRP。利用SPSS11.5统计学软件进行统计学分析。结果 RA湿热痹阻型患者外周血血清中IL-1、IL-6及TNF-α表达水平显著高于健康组血清,差异有统计学意义(t=12.25,10.56,8.758;P0.05);RA湿热痹阻型患者关节液中IL-1、IL-6及TNF-α的表达水平显著高于外周血血清,差异有统计学意义(t=4.35,3.09,2.496;P0.05);RA湿热痹阻型患者关节液中IL-1、IL-6及TNF-α表达水平明显高于骨性关节炎关节液,差异有统计学意义(t=3.47,2.46,2.51;P0.05)。RA湿热痹阻型患者外周血血清和关节液中IL-1、IL-6及TNF-α的表达与ESR、CRP、DAS28无相关性(P0.05)。结论 RA湿热痹阻型患者外周血和关节液中IL-1、IL-6及TNF-α的异常升高可能参与了RA的发生发展。     

泌乳素促进类风湿关节炎患者外周血单个核细胞分泌白细胞介素-6

目的:探讨类风湿关节炎(RA)患者血清泌乳素(PRL)水平与疾病活动程度的关系,以及PRL促进外周血单个核细胞(PBMCs)分泌白细胞介素-6(IL-6)的机制。方法:收集我院2015年3月至9月40例初治RA患者临床及实验室资料。采用化学发光免疫分析法(CLIA)检测血清PRL水平,ELISA检测IL-6水平,RT-q PCR检测泌乳素受体(PRLR)mRNA的表达,Western blot法检测MAPK通路相关蛋白p-p38的蛋白水平。结果:RA患者血清PRL水平明显升高(P0.01),活动期RA患者PRL水平明显高于非活动期RA患者(P0.01)。PRL水平与DAS28评分、ESR和CRP呈正相关(P0.01)。RA患者PBMCs中PRLR水平明显升高(P0.01)。PRL可诱导PBMCs分泌IL-6,siRNA沉默PRLR或采用MAPK通路抑制剂可抑制IL-6的产生。结论:RA患者血清PRL升高与DAS28评分、ESR和CRP呈正相关,PRL可作为预测RA严重程度的指标。PRL通过与PRLR相互作用,激活p38 MAPK通路,从而促进IL-6分泌。     

类风湿关节炎患者血清炎性因子、ANCA水平与血管内皮损伤标志物的相关性分析

目的:探讨类风湿关节炎(RA)患者血清炎性因子及抗中性粒细胞胞浆抗体(ANCA)水平与血管内皮损伤的相关性。方法:106例RA患者,分为活动组(83例)和缓解组(23例),55例健康人群作为对照,采用ELISA检测各组血清炎性因子白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)及血管内皮损伤标志物-血管性血友病因子(vWF)、可溶性细胞间黏附分子-1(sI-CAM-1)及血管内皮黏附分子-1(sVCAM-1)水平;采用间接免疫荧光法(IIF)检测各组血清ANCA阳性率。比较各组上述指标水平差异,分析两组RA患者炎性因子水平、ANCA阳性率与血管内皮损伤标志物水平的相关性。结果:RA活动组IL-6、TNF-α、vWF、sICAM-1、sVCAM-1血清水平均高于对照组(P<0.05);RA缓解组IL-6、vWF水平均低于RA活动组(P<0.05),但vWF、sVCAM-1水平仍显著高于对照组(P<0.01);RA患者IL-6、IL-1β、IL-17与血管内皮损伤标志物有不同程度的相关性;RA患者活动组ANCA阳性率为32.5%,显著高于对照组(P<0.01);ANCA阳性患者vWF水平高于ANCA阴性患者(P<0.05)。结论:RA活动期患者存在较明显血管内皮损伤,这种损伤与高水平的炎性因子及ANCA阳性表达有关。     

RA患者血清FFA、hs-CRP及TNF-α的水平变化与胰岛素抵抗的关系

目的：研究类风湿性关节炎（RA）患者血清游离脂肪酸（FFA）、高敏C-反应蛋白（hs-CRP）和肿瘤坏死因子（TNF-α）水平的变化及其与胰岛素抵抗的关系。方法：测定92例RA患者（稳定期53例,活动期39例）及50例正常人血清FFA、空腹胰岛素（fINS）、空腹血糖（fPS）,同时检测hs-CRP、TNF-α、血脂等指标,并计算胰岛素敏感指数（ISI）、稳态模型胰岛素抵抗指数（Homa-IR）,分析FFA水平的变化与胰岛素抵抗的关系。结果：非活动期和活动期RA患者,FFA、hs-CRP、TNF-α、Homa-IR、TG和LP（α）水平均较正常对照组显著升高（P〈0.05或P〈0.01）,且活动期RA组FFA、hs-CRP、TNF-α、fINS、Homa-IR、TG和LP（α）水平较非活动期RA患者明显升高（P〈0.05或P〈0.01）;直线相关分析显示,血清FFA水平与hs-CRP、TNF-α、fINS、Homa-IR、TG和LP（α）呈正相关（P〈0.01）,与ISI呈负相关（P〈0.01）。结论：RA患者血清FFA水平明显升高,且与hs-CRP、TNF-α及胰岛素抵抗密切相关。     

慢性乙型肝炎患者不同疾病阶段的血清细胞因子水平研究

目的探讨不同疾病阶段的慢性乙型肝炎(CHB)患者血清细胞因子水平变化情况及其可能的临床意义。方法 CHB患者98例和正常对照组20例入组本研究,依据HBV感染后的自然史将CHB患者分为免疫清除期患者(活动组)和非活动期患者(非活动组),采用Luminex液相芯片技术检测血清IL-2、IL-4、IL-6、IL-8、IL-10、GM-CSF、IFN-γ和TNF-α水平,并分析各组细胞因子的变化情况和与临床指标的相关性。结果除IL-10以外,IL-2、IL-4、IL-6、IL-8、GM-CSF、IFN-γ和TNF-α在3组间差异具有统计学意义(P<0.01),其中,非活动组IL-2、IL-4、IL-8、GM-CSF、IFN-γ和TNF-α水平高于对照组,活动组IL-2、IL-6、IL-8、GM-CSF和TNF-α水平高于对照组,活动组IL-4、IL-8和IFN-γ水平低于非活动组,差异有统计学意义(P<0.05);另外,IL-6、IL-8与ALT、AST、TBil之间显著相关(P<0.05);而其余细胞因子与生化指标、HBV-DNA载量和HBsAg之间无明显相关性。结论慢性HBV感染者血清中的多种细胞因子表达增加,其中免疫清除期以炎性细胞因子升高为主,非活动期以抗炎和Th1型细胞因子升高为主,因此,检测血清细胞因子对了解患者机体免疫状态和疾病严重程度有重要意义。     

活动期类风湿关节炎患者血清及关节液白细胞介素-17水平变化及与有关实验室指标的关系

目的:分析类风湿关节炎(RA)患者外周血和关节液中T辅助细胞17(Thl7)相关细胞因子白介素-17(IL-17)水平,探讨其在RA中的变化特点及与实验室指标的相关性.方法:用ELISA检测50例活动期RA患者血清和其中15例关节液以及30例正常人血清IL-17水平.同时测定RA患者血清超敏C反应蛋白(hs-CRP)、...     

肝硬化并自发性腹膜炎患者瘦素的变化及临床意义

目的:研究肝硬化并发自发性腹膜炎(SBP)患者血清及腹水中瘦素水平的变化和临床意义,并探讨其与TNF-α、IL-6的关系.方法:采用放射免疫法测定67例肝硬化腹水患者(SBP组32例,漏出液组35例)血清及腹水瘦素水平,同时采用双抗体夹心ELISA法测定血清及腹水的INF-α、IL-6水平.结果:SBP组血清及腹水瘦素、TNF-α、IL-6水平明显高于漏出液组(P<0.01),且腹水的瘦素、TNF-α、IL-6水平又高于血清(P<0.01和P<0.05);感染控制后,血清和腹水瘦素、TNF-α、IL-6水平明显降低(P<0.01和P<0.05);SBP治疗无效组的初始血清和腹水瘦素、TNF-α、IL-6水平明显高于治疗有效组(P<0.01和P<0.05);肝硬化患者血清和腹水的瘦素与TNF-α、IL-6变化呈正相关.结论:肝硬化并发SBP时血清和腹水中的瘦素、TNF-α、IL-6明显升高,临床上检测血清和腹水的瘦素、TNF-α、IL-6水平对SBP的早期诊断、疗效判断及预后评估均有意义.     

白细胞介素-37在类风湿性关节炎患者血清表达水平的研究

目的 通过检测类风湿性关节炎(RA)患者血清中细胞因子白细胞介素(IL)-37、肿瘤坏死因子-α(TNF-α)、IL-18、炎性指标红细胞沉降率以及C-反应蛋白(C-reactionprotein,CRP)水平,观察RA患者临床数据包括压痛关节数,肿胀关节数以及DAS28评分等,探讨RA患者血清IL-37水平升高的意义以其在RA发病机制中可能的作用.方法 80例RA患者、80例健康对照患者,通过酶联免疫吸附试验(ELISA)法检测其血清中细胞因子水平.结果 RA患者血清中IL-37[(40.33±11.25)pg/mL]、TNF-α[(110.41 ±35.37) pg/mL]、IL-18[(121.73±29.22) pg/mL]水平以及红细胞沉降率(ESR)[(42.31±15.02) mm./h]、CRP[(38.31±17.22) mg/L]水平明显高于对照组IL-37[(18.21±5.72) pg/mL]、TNF-α[(30.19±6.82) pg/mL]、IL-18[(55.47±7.29) pg/mL]水平,组间差异有统计学意义(P＜0.05).IL-37的表达与TNF-α、IL-18水平呈正相关(相关系数r=0.981,P=0.001).结论 IL-37在RA患者体内高表达并与其它几种炎性因子的表达具有相关性,IL-37可能作为炎性抑制因子参与了RA的发生、发展.     

阻塞性睡眠呼吸暂停综合征患者血清IL-6、TNF-α测定的临床意义

目的:探讨阻塞性睡眠呼吸暂停综合征(OSAS)患者血清IL-6、TNF-α水平测定的临床意义。方法:68例OSAS患者分为轻度组(36例)和中、重度组(32例),同时选取健康对照者30例,采用酶联免疫吸附法(ELISA)测定其血清IL-6、TNF-α水平,同时检测睡眠呼吸暂停低通气指数(AHI)及夜间最低血氧饱和度(SaO2),并进行相关性分析。32例中、重度OSAS患者经鼻持续正压通气(nCPAP)治疗,于治疗前及治疗后监测AHI、SaO2、IL-6和TNF-α水平。结果:OSAS患者AHI和血清IL-6、TNF-α水平显著高于对照组(P<0.01),平均SaO2和最低SaO2与对照组相比明显降低(P<0.01)。中、重度OSAS患者经nCPAP后AHI和最低SaO2明显改善,血清IL-6和TNF-α水平均较治疗前明显降低(P<0.01)。OSAS患者血清IL-6、TNF-α水平分别与AHI呈正相关(r=0.75,r=0.82,P<0.01);与SaO2呈负相关(r=-0.65、r=-0.74,P<0.01)。结论:血清IL-6、TNF-α参与了OSAS的发病,而且与病情严重程度密切相关。     

Interleukin 2 inhibitor in synovial fluid.

Since evidence for the presence of IL-2 activity in rheumatoid synovial fluid is conflicting, we have assayed IL-2 activity in synovial fluid from patients with rheumatoid arthritis (RA) and other articular diseases (OAD). Using the IL-2-dependent murine T cell line CTLL, IL-2 activity was not demonstrable in synovial fluid tested at concentrations ranging from 50% to 0.02%. There was an inhibitory effect on IL-2 activity in the bioassay of synovial fluid from 16 of the 22 patients with RA and 15 of the 16 with OAD. This inhibitory activity was heat-labile, precipitable by ammonium sulphate, reversible with excess IL-2 and was not significantly altered by preincubation of synovial fluid with CTLL. The mean inhibitory activity of synovial fluid from patients with RA was significantly reduced in comparison with that of synovial fluid from patients with OAD. Sera also had an inhibitory effect on IL-2 activity; however sera from patients with RA were less inhibitory than control sera but were more inhibitory than sera from patients with systemic lupus erythematosus. The deficiency in synovial fluid of an inhibitor of IL-2 activity may be relevant to the pathogenesis of RA.     

过敏性紫癜患者血清IL-34水平的变化及意义

目的:探讨过敏性紫癜(Henoch-Schoenlein purpura,HSP)患者急性期血清中IL-34 的表达及意义。方法:选取HSP 患者38 例,同期匹配的健康人21 例作为对照组,采用酶联免疫吸附法(ELISA)及化学发光法检测血清中IL-34、IL-6、TNF-β表达水平;采用相关分析法分析IL-34 与患者临床资料指标的关系以及与IL-6、TNF-β表达的相关性。结果:HSP 患者急性期血清IL-34、IL-6、TNF-β水平均较正常对照组增高,差异具有统计学意义(P<0.001);血清IL-34 和超敏C 反应蛋白(hs-CRP)、IL-6 水平之间呈正相关(分别是r =0.453,P =0.004;r =0.469,P =0.003)。结论:IL-34 可能参与过敏性紫癜的致病过程;可能与过敏性紫癜促炎因子的异常表达有关,促进血管炎症的发生发展。     

TNF-α上调单核巨噬细胞MMP-9的活性与类风湿关节炎关节破坏的关系

目的： 探讨TNF-α对单核巨噬细胞基质金属蛋白酶9（MMP-9）的表达与酶活性的影响以及与类风湿关节炎患者关节破坏的关系。方法：用双抗体夹心ELISA法检测类风湿关节炎患者组（RA）和对照组血清和关节滑液中TNF-α、MMP-9的含量,观察MMP-9与X线表现积分（Larsen）的关系。体外将佛波酯（TPA）和不同浓度（0、1、10、20 μg/L）TNF-α共同孵育THP-1细胞24 h后,运用Western blotting方法检测MMP-9蛋白的表达,明胶酶谱法检测MMP-9活性,侵蚀小室法观察分化前后THP-1细胞的侵蚀力。结果：RA患者组血清和关节滑液中TNF-α、MMP-9的水平明显高于对照组（P＜0.05）,且血清和滑液MMP-9与Larsen积分显著相关（r＝0.37和r=0.32,P＜0.01）;体外细胞实验中,TNF-α上调分化的THP-1中MMP-9的表达和酶活性,并且增强分化的THP-1细胞的侵蚀性,并与TNF-α呈浓度依赖性。结论：TNF-α上调单核巨噬细胞MMP-9表达及活化,增强了炎症细胞的侵蚀力,可能在RA关节破坏机制中起着重要的作用。     

The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis (RA)

The aim of this study was to investigate the role of IL-12 in patients with RA. IL-12 (p70) and its associated cytokines were measured in sera and synovial fluid (SF) using an enzyme-linked immunosorbent method. Seven American College of Rheumatology (ACR) core set measures as well as IL-12 levels were sequentially monitored at the commencement and 4 months after treatment with a low-dose steroid and disease-modifying anti-rheumatic drugs (DMARDs). In sera, 64 (42.2%) of 152 RA patients had detectable concentrations of IL-12 (p70), whereas one (1.4%) of 69 osteoarthritis (OA) patients and five (10%) of 50 healthy controls had detectable IL-12 (P < 0.001). The median level of circulating IL-12 was also higher in RA patients (P < 0.001). In SF, the number of patients with detectable IL-12 and the median IL-12 levels were significantly higher in RA patients (n = 53) than in OA patients (n = 22). In paired samples (n = 53) of sera and SF from RA patients, IL-12 levels were higher in the SF than in sera (P < 0.001). Patients with detectable IL-12 (n = 51) in sera had higher tender joint scores (P = 0.003), swollen joint scores (P < 0.001) and C-reactive protein (CRP; P = 0.036), than those without (n = 55). Four months after treatment with DMARDs, the improved group showed a larger IL-12 decrease than the non-improved group (P = 0.017). The levels of IL-12 correlated positively with those of IL-2, interferon-gamma, IL-6, and tumour necrosis factor-alpha, but were correlated inversely with those of IL-10. Our results demonstrate that IL-12 levels reflect RA disease activity and that IL-12 is involved in the production of proinflammatory cytokines. An IL-12 blockade could be useful for the treatment of RA.     

Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis

The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 ± 464.0 pg/mL) than in healthy controls (96.0 ± 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1β (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-na?ve RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.     

Interleukin-6 in synovial fluid from patients with arthritis

Synovial fluid and serum from patients with rheumatoid arthritis, other inflammatory arthritides, and traumatic arthritis were assayed for the presence of interleukin-6 (IL-6) by means of an IL-6-dependent mouse hybridoma cell line. The cytokine was detected in all the samples of synovial fluid (range 50-22000 U/ml). IL-6 in synovial fluid was positively correlated (r = 0.58, P = 0.03) with the erythrocyte sedimentation rate in patients with inflammatory arthritis. In serum, the concentration of IL-6 was slightly elevated in some patients with rheumatoid arthritis. The results demonstrate that IL-6 is released into synovial fluid in joints affected by arthritis, and there appears to be an association between the levels of IL-6 and disease activity.     

Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA)

PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein (CRP)) and of an unrelated N-terminal domain. Unlike the classical pentraxins, the long pentraxin PTX3 is expressed in response to IL-1beta and tumour necrosis factor-alpha (TNF-alpha), but not to IL-6, in various cell types. The present study was designed to investigate the expression of PTX3 in RA. Dissociated RA and osteoarthritis (OA) type B synoviocytes were cultured in the presence and in the absence of inflammatory cytokines. PTX3 mRNA expression in synoviocytes was evaluated by Northern analysis. PTX3 protein levels in synovial cell cultures and synovial fluid were estimated by ELISA, and PTX3 distribution in synovial tissues by immunohistochemical techniques. OA synoviocytes were induced to express high levels of PTX3 mRNA by TNF-alpha, but not by other cytokines including IL-1beta and IL-6. RA synoviocytes, unlike OA synoviocytes, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in RA synoviocytes was not modified by anti-TNF-alpha antibodies, IL-1 receptor antagonist or a combination of the two agents. In contrast, interferon-gamma and transforming growth factor-beta inhibited PTX3 constitutive expression in RA synoviocytes. The joint fluid from RA patients contained higher levels of immunoreactive PTX3 than controls and the synovial tissue contained endothelial cells and synoviocytes positive for PTX3 by immunohistochemistry. In conclusion, PTX3 may play a role in inflammatory circuits of RA, and its relevance as a marker of disease activity deserves further study.     

IL-22在类风湿关节炎中的表达及临床意义

目的：探讨RA患者IL-22的表达水平并分析其临床意义。方法：流式细胞术检测RA患者（50例）、OA患者（15例）、健康对照组（15例）外周血及RA关节滑液Th22细胞所占比例,ELISA法检测血清及RA关节滑液中IL-22水平。检测RA患者疾病活动性、临床指标、骨破坏情况,分析其与IL-22水平相关性。两组间比较用t检验,相关性分析采用Pearson直线相关分析法,多组样本比较用Kruskal-Wallis H检验。结果：RA患者外周血中Th22细胞比例高于OA组（t=2.290,P=0.021）及健康对照组（t=2.524,P=0.015）;RA患者血清IL-22水平高于OA患者（t=2.560,P=0.014）及健康对照组（t=2.768,P=0.009）。RF阳性RA血清IL-22水平高于RF阴性RA（t=2.322,P=0.035）。抗CCP抗体阳性RA血清IL-22水平高于抗CCP抗体阴性RA（t=2.504,P=0.015）。RA血清IL-22水平与ESR、RF、DAS28评分呈正相关关系（r分别为0.312、0.314、0.332,P<0.05）。RA患者血清IL-22水平随骨侵蚀的加重呈递增趋势,X线不同分期之间差异有统计学意义（H=9.14, χ²_0.05（3）=7.81,H>χ²_0.05(3),P<0.05)。有关节积液RA患者血清IL-22水平高于无关节积液RA患者（t=2.587,P=0.012）,关节滑液IL-22水平高于血清（t=2.668,P=0.011）,与关节滑液Th22细胞比例无相关性（r=0.287,P=0.065）。结论：RA患者血清及关节滑液IL-22水平增高,与疾病活动性及骨破坏相关,可成为病情评估与骨破坏的指标。IL-22可能为RA治疗的新靶点。