类风湿关节炎患者IL-18检测的影响因素分析

目的探讨不同的保存时间、温度对类风湿关节炎(RA)患者外周血与关节积液IL-18水平的影响。方法将12例RA患者的血清与关节积液按照不同保存时间与温度条件分为A组(血清,室温0h)、B组(全血,室温36h)、C组(全血,室温72h)、D组(全血,4℃72h)、E组(血清,室温72h)、F组(关节液,室温0h)、G组(关节液,室温72h),用ELISA检测各组IL-18浓度变化。结果 B、D、E组IL-18浓度明显高于A组(均P<0.05);F组IL-18浓度与A组比较差异无统计学意义(P>0.05)。非参数两关联样本检验显示C组IL-18浓度明显高于A、B、D组;G组IL-18浓度明显高于F组(P<0.05)。结论外周血及关节积液IL-18水平变化趋势一致,IL-18检测受时间和温度影响,且温度影响更显著。     

IL-1β在痛风性关节炎中的致炎作用及临床意义

近年来国内外许多学者对痛风性关节炎与炎性因子的关系进行了探讨,大多数观点认为急性痛风性关节炎是由于体内沉积的尿酸盐结晶促使单核巨噬细胞黏附渗出,并吞噬尿酸盐微晶体后分泌炎症因子,从而诱发的免疫反应。IL-1β作为体内重要的致炎因子,在许多自身免疫性疾病中发挥着重要作用,也在尿酸盐晶体沉积引起的痛风性关节炎的关节损害过程中扮演了关键角色。随着对IL-1β在痛风性关节炎发病机制中作用的深入研究,应用抗IL-1类生物制剂治疗痛风已受到医学界高度关注,为治疗痛风带来了新希望,有助于进一步改善痛风的结局。     

类风湿因子阴性类风湿关节炎患者血清抗瓜氨酸肽或蛋白抗体、IL-10及IL-18检测分析

目的探讨抗瓜氨酸肽或蛋白抗体(ACPAs)、白细胞介素(IL)-10和IL-18在类风湿因子(RF)阴性类风湿性关节炎(RA)诊断中的临床意义。方法分别收集RF阴性的RA患者56例、系统性红斑狼疮(SLE)患者40例和RF阴性骨关节炎(OA)患者44例的血清,采用间接免疫荧光法检测抗角蛋白抗(AKA),采用酶联免疫吸附法检测anti-Sa、抗环瓜氨酸(CCP)多肽抗体、IL-10和IL-18。结果 AKA、anti-Sa和抗CCP抗体在RF阴性RA、SLE和OA患者中的阳性率分别为33.9%、50.0%和64.3%,抗CCP抗体阴性、RF阴性RA患者IL-10水平低于抗CCP抗体阳性、RF阴性RA患者(P<0.05),而IL-18则相反(P<0.05)。结论 ACPAs检测有助于提高RF阴性RA患者的诊断率。早期的炎症因子失衡可能与RA早期病变有关。IL-10、IL-18检测对于抗CCP抗体阴性、RF阴性临床可疑RA患者具有一定的早期预测价值和鉴别诊断价值。     

A role for IL-18 in human neutrophil apoptosis

Decreased neutrophil apoptosis is associated with persistent inflammation, the severity of which correlates with serum IL-18 levels. IL-18 receptors as well as Toll-like receptors, including Toll-like receptor 4, a receptor for LPS, possess a highly conserved intracellular domain called "Toll-IL-1R domain" and activate overlapping signaling pathways. Here, we show that IL-18 modulates neutrophil apoptosis and compare its mechanism of action with LPS. We found that both IL-18 and LPS decreased neutrophil apoptosis in a similar dose- and time-dependent fashion. However, pretreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 increased apoptosis more effectively in IL-18- than in LPS-stimulated cells, whereas the ERK inhibitor PD98059 had the same effect in both. In contrast, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 had no influence on apoptosis at all. Neutrophils constitutively expressed mRNA for IL-18 receptor beta, but little or no receptor alpha, both of which increased during coculture with either IL-18 or LPS in a time- and dose-dependent manner. Of the Bcl-2 family, antiapoptotic A1/Bfl-1 tended to increase on IL-18 and LPS stimulation, but was further increased despite increased apoptosis in the presence of MAPK inhibitors. Thus, human neutrophils can express mRNA for IL-18 receptors alpha and beta, and IL-18, like LPS, inhibits neutrophil apoptosis by activating PI3K and ERK pathways but not p38MAPK. However, PI3K may play more important role(s) in IL-18- than in LPS-induced inhibition of apoptosis. Mitogen-activated protein kinases seem to mediate antiapoptotic signals through factors other than Bcl-2 gene family expression.     

类风湿性关节炎患者IL-15、IL-18的水平变化及意义

目的 研究类风湿性关节炎(RA)患者血清IL-15、IL-18的变化及其临床意义.方法 收集30例RA患者,以20例骨关节炎(OA)患者和10例健康体检者作对照.采用双抗体夹心酶联免疫吸附法测定血清IL-15、IL-18的水平,并测定类风湿因子和C反应蛋白.结果 RA患者的血清IL-15、IL-18的含量明显高于OA组及健康体检组,RA患者的类风湿因子明显高于对照组,C反应蛋白的含量在各组间差异无统计学意义.结论 IL-15、IL-18在RA患者的疾病发展过程中发挥着重要作用,阻断IL-15、IL-18的生物活性,为靶向治疗RA患者提供了新思路.     

IL—12及Th1／Th2型细胞因子在类风湿关节炎中的作用

目的　探讨IL 12在类风湿关节炎 (RA)中的作用 ,患者Th1/Th2型细胞因子的表达及其与疾病的活动度的相关性。方法　应用ELISA对 12 8例RA患者的血清及滑膜液 (SF)IL 12水平和Th1/Th2型细胞因子水平进行了跟踪检测 ,并作了比较 ,且与疾病活动性的关系进行了分析。结果　在RA、其他骨关节疾病及正常人中IL 12水平存在明显差别 ,血清IL 12水平同CRP、RF明显相关 ,其相关系数 (r)分别为 0 .5 38、0 .5 5 7;在药物治疗后改善组患者中 ,治疗前后的IL 12水平存在明显差别 ,同时血清及SF中IL 12阳性组与阴性组患者细胞因子水平存在明显差异 ,血清中IL 12水平与IL 6、IL 10、IFNγ、IFNγ/IL 10水平之间存在明显的相关性 (r分别为 0 .5 6 5、- 0 .5 5 0、0 .5 6 8、0 .817) ,而SF中 ,IL 12水平与IL 6 (r =0 .4 89)、IFNγ(r =0 .4 97)存在明显相关。结论　研究证实 ,在RA中存在Th1/Th2型细胞因子表达不平衡 ,IL 12水平能反映RA的病情 ,并与IL 6、IFNγ等前炎症因子相关 ,降低IL 12水平有助于治疗RA。     

IL-12及Th1/Th2型细胞因子在类风湿关节炎中的作用

目的探讨IL-12在类风湿关节炎(RA)中的作用,患者Th1/Th2型细胞因子的表达及其与疾病的活动度的相关性.方法应用ELISA对128例RA患者的血清及滑膜液(SF)IL-12水平和Th1/Th2型细胞因子水平进行了跟踪检测,并作了比较,且与疾病活动性的关系进行了分析.结果在RA、其他骨关节疾病及正常人中IL-12水平存在明显差别,血清IL-12水平同CRP、RF明显相关,其相关系数(r)分别为0.538、0.557;在药物治疗后改善组患者中,治疗前后的IL-12水平存在明显差别,同时血清及SF中IL-12阳性组与阴性组患者细胞因子水平存在明显差异,血清中IL-12水平与IL-6、IL-10、IFNγ、IFNγ/IL-10水平之间存在明显的相关性(r分别为0.565、-0.550、0.568、0.817),而SF中,IL-12水平与IL-6(r=0.489)、IFNγ(r=0.497)存在明显相关.结论研究证实,在RA中存在Th1/Th2型细胞因子表达不平衡,IL-12水平能反映RA的病情,并与IL-6、IFNγ等前炎症因子相关,降低IL-12水平有助于治疗RA.     

类风湿关节炎患者血清 ACCP 抗体、MMP-3、IL-17、IL-18的水平变化及意义

目的：探讨抗环瓜氨酸肽（ACCP）抗体、基质金属蛋白酶-3（MMP-3）、白细胞介素-17（IL-17）、白细胞介素-18（IL-18）在类风湿关节炎（RA）患者血清中的变化和意义。方法酶联免疫吸附试验（ELISA）法检测80例 RA 患者、32例骨关节炎（OA）患者和32例健康对照外周血血清 ACCP 抗体、MMP-3、IL-17、IL-18水平,进行统计分析。结果RA 组 ACCP 抗体、MMP-3、IL-17、IL-18显著高于 OA 组和健康对照组;RA 低、中、高活动组 ACCP 抗体、MMP-3、IL-17、IL-18高于稳定组,RA 组 ACCP 抗体、MMP-3、IL-17、IL-18、疾病活动评价分数（DAS28）、C-反应蛋白（CRP）、红细胞沉降率（ESR）都升高;ACCP 抗体阳性组 MMP-3、IL-17、IL-18、DAS28高于阴性组;RA 组 ACCP 抗体、MMP-3、IL-17、IL-18之间正相关;ACCP 抗体、MMP-3、IL-17、IL18与 RA低、中、高活动组监测指标 CRP、DAS28呈正相关。结论MMP-3、IL-17、IL-18参与 RA 的发生、发展过程;ACCP 抗体、MMP-3、IL-17、IL-18的检测对 RA 患者病情活动的判断和疾病的防治有一定的价值。     

类风湿关节炎患者血清sFas、sFasL和IL-18水平及意义

目的　探讨类风湿关节炎 (RA)患者血中可溶性Fas(sFas)、可溶性Fas配体 (sFasL)和白细胞介素 18(IL 18)水平及意义。方法　应用双抗体夹心酶联免疫吸附试验 (ELISA)和速率散射比浊法检测 70例RA患者血中sFas、sFasL、IL 18和类风湿因子 (RF)、C 反应蛋白 (CRP)含量。结果　RA患者sFas、sFasL、IL 18、RF、CRP含量分别为 ( 3.75± 1.79)ng/ml、( 12 15± 10 17)pg/ml、( 6 6 .6± 4 9.6 ) pg/ml、( 4 87±6 6 1)IU/ml、( 2 .75±4 .14 )mg/dl,与对照组 [( 2 .37± 1.2 9)ng/ml、( 4 43± 2 4 5 ) pg/ml、( 32 .2± 2 0 .5 ) pg/ml、<30IU/ml、<0 .0 1mg/dl]相比 ,差异有显著性 (P <0 .0 5 )。sFasL与CRP、RF呈正相关 (r =0 .5 36 ,r =0 .394 ,P <0 .0 5 ) ,sFas与IL 18呈正相关 (r =0 .80 8,P <0 .0 1)。结论　sFas、sFasL、IL 18与RA的发病过程有关     

类风湿关节炎患者血清sFas、sFasL和IL-18水平及意义

目的探讨类风湿关节炎(RA)患者血中可溶性Fas(sFas)、可溶性Fas配体(sFasL)和白细胞介素-18(IL-18)水平及意义.方法应用双抗体夹心酶联免疫吸附试验(ELISA)和速率散射比浊法检测70例RA患者血中sFas、sFasL、IL-18和类风湿因子(RF)、C-反应蛋白(CRP)含量.结果 RA患者sFas、sFasL、IL-18、RF、CRP含量分别为(3.75±1.79) ng/ml、(1 215±1 017) pg/ml、(66.6±49.6) pg/ml、(487±661) IU/ml、(2.75±4.14) mg/dl,与对照组[(2.37±1.29) ng/ml、(443±245) pg/ml、(32.2±20.5) pg/ml、<30 IU/ml、<0.01 mg/dl]相比,差异有显著性(P<0.05).sFasL与CRP、RF呈正相关(r=0.536,r=0.394,P<0.05),sFas与IL-18呈正相关(r=0.808,P<0.01).结论 sFas、sFasL、IL-18与RA的发病过程有关.     

A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.     

外周血白细胞介素-18与类风湿性关节炎相关性研究

目的：探讨外周血白细胞介素-18（IL-18）水平与类风湿性关节炎（RA）的相关性方法：应用酶联免疫吸附技术（ELSIA）检测168例健康体检者和60例稳定期、60例活动期RA患者的IL—18水平．同时检测WBC、RBC、HGB、PLT、血沉（ESR）、抗链球菌溶血素“O”（ASO）、类风湿因子（RF）、C反应蛋白（CRP）等实验室指标．结果：健康体检者、RA活动期与稳定期患者IL-18水平比较差异均无统计学意义（P〉0．05）：RA患者WBC、PLT、ESR、RF、CRP水平均显著高于健康体检者（P〈0．001）。RA活动期患者PLT、ESR、CRP水平均显著高于稳定期（P〈0．05）．结论：外周血IL-18可能与RA免疫炎症无关．     

Epigenetic regulator UHRF1 orchestrates proinflammatory gene expression in rheumatoid arthritis in a suppressive manner

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation with aberrant epigenetic alterations, eventually leading to joint destruction. However, the epigenetic regulatory mechanisms underlying RA pathogenesis remain largely unknown. Here, we showed that ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is a central epigenetic regulator that orchestrates multiple pathogeneses in RA in a suppressive manner. UHRF1 expression was remarkably upregulated in synovial fibroblasts (SFs) from arthritis model mice and patients with RA. Mice with SF-specific Uhrf1 conditional knockout showed more severe arthritic phenotypes than littermate controls. Uhrf1-deficient SFs also exhibited enhanced apoptosis resistance and upregulated expression of several cytokines, including Ccl20. In patients with RA, DAS28, CRP, and Th17 accumulation and apoptosis resistance were negatively correlated with UHRF1 expression in synovium. Finally, Ryuvidine administration stabilized UHRF1 ameliorated arthritis pathogeneses in a mouse model of RA. This study demonstrated that UHRF1 expressed in RA SFs can contribute to negative feedback mechanisms that suppress multiple pathogenic events in arthritis, suggesting that targeting UHRF1 could be one of the therapeutic strategies for RA.     

Evidence that cytokines play a role in rheumatoid arthritis

A large number of cytokines are active in the joints of patients with rheumatoid arthritis (RA). It is now clear that these cytokines play a fundamental role in the processes that cause inflammation, articular destruction, and the comorbidities associated with RA. Following the success of TNF-α blockade as a treatment for RA, other cytokines now offer alternative targets for therapeutic intervention or might be useful as predictive biomarkers of disease. In this Review, we discuss the biologic contribution and therapeutic potential of the major cytokine families to RA pathology, focusing on molecules contained within the TNF-α, IL-1, IL-6, IL-23, and IL-2 families.     

Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis

Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.     

Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis

Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.