胃癌患者血清可溶性白细胞介素－2受体初步研究

应用双抗体夹心ＥＬＩＳＡ法对３０例胃癌患者血清ｓＩＬ－２Ｒ水平进行测定。结果表明，胃癌患者血清ｓＩＬ－２Ｒ水平明显高于正常对照（Ｐ＜０．０１）及慢性良性胃病患者（Ｐ＜０．０５）；Ⅲ－Ⅳ期患者血清ｓＩＬ－２Ｒ水平显著高于Ⅰ－Ⅱ期患者（Ｐ＜０．０５）；低度分化者较中度分化者ｓＩＬ－２Ｒ水平明显升高（Ｐ＜００１）；贲门癌患者ｓＩＬ－２Ｒ水平较胃窦（体）癌者高，但未达到统计学差别（Ｐ＞０．０５）；胃癌根治术后一周血清ｓＩＬ－２Ｒ水平较术前升高（Ｐ＜０．０１），术后二周血清ｓＩＬ－２Ｒ较术前明显降低（Ｐ＜０．０１），与正常人相比无明显差异（Ｐ＞００５）。结果提示血清ｓＩＬ－２Ｒ测定可作为胃癌患者病情判断、观察疗效及估价预后新的生物学指标。     

过敏性哮喘患者细胞因子对IgE生成机制的探讨

对３０例过敏性哮喘患者发作期和缓解期及３０例健康成年人的外周血，采用ＥＬＩＳＡ双抗体夹心法，测定血清ＩｇＥ，可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和白细胞介素－４（ＩＬ－４）水平，生物学方法测定血清ＩＬ－２水平和３Ｈ－ＴｄＲ掺入法定量测定血清ＩＬ－６。结果：过敏性哮喘患者发作期血清ＩｇＥ、ｓＩＬ－２Ｒ、ＩＬ－４和ＩＬ－６水平明显升高，与缓解期和对照组有明显差异（Ｐ＜０．０１），而发作期血清ＩＬ－２水平明显下降，与缓解期和对照组有明显差异（Ｐ＜０．０１），且血清ＩｇＥ分别与ｓＩＬ－２Ｒ和ＩＬ－４水平有明显正相关（Ｐ均＜０．０１），与ＩＬ－２水平有明显负相关（Ｐ＜０．０１）。说明ＩｇＥ合成增加是过敏性哮喘的关键，细胞因子有促进Ｂ细胞合成ＩｇＥ的作用，并且直接参与过敏性哮喘气道炎症的形成。     

可溶性白介素2受体与急性心肌梗塞相关性的研究

本研究采取双抗体夹心ＥＬＩＳＡ法测定３２例急性心肌梗塞患者血清可溶性白介素２受体（ｓＩＬ－２Ｒ）和肌酸激酶（ＣＫ）结果显示：急性心肌梗塞的ｓＩＬ－２Ｒ和ＣＫ明显高于恢复期的患者及正常对照组（ｎ＝４０）（Ｐ＜０．００１，Ｐ＜０．００１），而恢复期与正常对照组无显著差异（Ｐ＞０．０５）；ｓＩＬ－２Ｒ水平与急性心肌梗塞的面积呈正相关（Ｐ＜０．００１，Ｐ＜０．０５）；无并发症的急性心肌梗塞与伴有并发症的急性心肌梗塞的ｓＩＬ－２Ｒ、ＣＫ有显著差异（Ｐ＜０．０５．Ｐ＜０．０１）．提示急性心肌梗塞患者存在免疫调节功能改变，显示ｓＩＬ－２Ｒ做为急性心肌梗塞患者病情监测、判断预后的指标。     

囊虫病患者 IL-2 及 sIL-2R 测定

应用四甲基偶氮唑盐（ＭＴＴ）法检测了３１例未经治疗的囊虫病患者外周血单个核细胞（ＰＢＭＣ）产生ＩＬ－２水平，同时用ＥＬＩＳＡ双抗体夹心法测定其血清中ｓＩＬ－２Ｒ水平，以３０例健康人作对照。实验结果显示，囊虫病患者ＰＢＭＣ产生ＩＬ－２水平明显低于正常人（Ｐ＜０．０５），而患者血清中ｓＩＬ－２Ｒ水平明显高于正常人（Ｐ＜０．０１）。本实验提示囊虫病患者外周血中低水平的ＩＬ－２及血清中高水平的ｓＩＬ－２Ｒ可能与患者细胞免疫功能低下有关。     

胃癌患者可溶性白细胞介素-2受体与肿瘤坏死因子-α水平的临床观察

为观察可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和肿瘤坏死因子－α（ＴＮＦ－α）对胃癌的诊断及估计预后的价值，应用酶联免疫双抗夹心法对７８例胃癌患者及对照者血清检测上述两种成分，进行临床观察。结果发现：胃癌患者血清ｓＩＬ－２Ｒ和ＴＮＦ－α水平明显高于胃良性疾病和正常人（均Ｐ＜０．０１）；胃癌Ⅲ、Ⅳ期高于Ⅰ、Ⅱ期（均Ｐ＜０．０１）；手术切除后（根治性或姑息性）ｓＩＬ－２Ｒ和ＴＮＦ－α显著下降（均Ｐ＜０．０１）；手术后复发或转移患者血清中ｓＩＬ－２Ｒ和ＴＮＦ－α含量升高（均Ｐ＜０．０１）；如果患者血清ｓＩＬ－２Ｒ含量高于１０００ｋＵ／Ｌ同时伴有ＴＮＦ－α持续高于１２０μｇ／Ｌ，预兆生存期短。提示监测胃癌患者血清ｓＩＬ－２Ｒ和ＴＮＦ－α水平对临床诊断、病情估计和预后有重要意义     

风湿性心脏病患儿血清sIL－2R水平变化及其临床意义

采用酶标记免疫吸附分析法检测４５例风湿性心脏病患儿及３０例正常儿童血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平．结果：风湿性心脏病活动期患儿血清ｓＩＬ－２Ｒ水平（７１１．６７±１６３．７８ｕ／ｍｌ）较非活动期的（３７３．８１±１５８．７０ｕ／ｍｌ）及对照组的（２８９．６７±１０２．４４ｕ／ｍｌ）高，差异有显著性（均Ｐ＜０．０１）；非活动期较对照组高，差异有显著性（Ｐ＜０．０５）；活动期心功能Ⅱ、Ⅳ级者血清ｓＩＬ－２Ｒ水平（８０１．６７±１４４．５９ｕ／ｍｌ）较心功能Ⅰ、Ⅱ级者（６２１．６７±１３２．３１ｕ／ｍｌ）高，差异有显著性（Ｐ＜０．０１），活动期血清ｓＩＬ－２Ｒ水平与血沉呈正相关（ｒ＝０．８２，Ｐ＜０．０１）．提示：风湿性心脏病非活动期患儿体内异常免疫反应可能尚在进行，抗风湿疗程可适当延长；血清ｓＩＬ－２Ｒ水平与病情及风湿活动有一定关系，可望成为疗效及风湿活动的观察指标之一．     

老年心衰患者血清sIL—2R及T细胞亚群的变化

目的研究老年心衰（ＨＦ）患者血清中可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）及Ｔ淋巴细胞亚群（Ｔ－ＬＳ）的变化及临床意义。方法血清ｓＩＬ－２Ｒ测定采用酶联免疫吸附双抗体夹心法，Ｔ－ＬＳ采用抗体致敏的红细胞花环法。检测４０例老年ＨＦ及３０例正常组血清ｓＩＬ－２Ｒ及Ｔ－ＬＳ的变化。结果老年ＨＦ患者血清ｓＩＬ－２Ｒ水平与正常组比较显著增高（Ｐ＜０．０５，Ｐ＜０．０１）；Ｔ－ＬＳ在老年ＨＦ与正常组比较显著下降（Ｐ＜０．０５，Ｐ＜０．０１）。结论血清ｓＩＬ－２Ｒ水平及细胞免疫低下可影响老年ＨＦ的发病及预后     

肺结核化疗前后血清可溶性白细胞介素－2受体测定

本文采用双抗体夹心法检测３５例病人化疗前后血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）浓度，结果：化疗前ｓＩＬ－２Ｒ血清浓度，高于健康对照组（Ｐ＜０．０１）和治疗后２个月（Ｐ＜０．０５）。随病情好转细胞免疫功能逐渐恢复，血清ｓｉＬ－２Ｒ亦随之趋于正常。可见测定血清ｓＩＬ－２Ｒ浓度，可为肺结核的诊断与病情监测提供参考指标。     

老年高血压病患者血清可溶性白介素2受体与临床分期相关性的观察

目的探讨老年高血压病患者血清中可溶性白介素－２受体（ｓＩＬ－２Ｒ）的水平，并比较老年高血压病不同临床分期的ｓＩＬ－２Ｒ变化。方法采用双抗体夹心（ＥＬＩＳＡ）法，对４６例老年高血压病人血清ｓＩＬ－２Ｒ的水平，与３０例正常人（ＮＣ）进行检测对比，并对其老年高血压病患者不同临床分期的ｓＩＬ－２Ｒ的水平进行观察。结果老年高血压病患者ｓＩＬ－２Ｒ水平明显高于对照组（Ｐ＜０．０１）；且随临床分期的增加而增高（Ｐ＜０．０１），有明显的正相关性。结论老年高血压病患者体内存在有免疫功能系乱，导致ｓＩＬ－２Ｒ的增高。ｓＩＬ－２Ｒ可作为临床观察老年高血压病的细胞免疫功能及病情判定的有效指标。     

胃癌患者血清可溶性白细胞介素—2受体初步研究

应用双抗体夹心ＥＬＩＳＡ法对３０例胃癌患者血清ＳＩＬ－２Ｒ水平进行测定，结果表明，胃癌患者血清ＳＩＬ－２Ｒ水平明显高于正常对照（Ｐ＜０．０１）及慢性良性胃病患者（Ｐ＜０．０５）；Ⅲ－Ⅳ期患者血清ＳＩＬ－２Ｒ水平显著高于Ｉ－ＩＩ期患者（Ｐ＜０．０５）；低度分化者较中度分化者ＳＩＬ－２Ｒ水平明显升高（Ｐ＜０．０１）；贲门癌患者ＳＩＬ－２Ｒ水平较胃窦（体）癌者高，但未达到统计学差别（Ｐ＞０．０５）；胃癌     

Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease

Interleukin-6 (IL-6) plays pathologic roles in immune-inflammatory diseases such as rheumatoid arthritis (RA) and Castleman disease. By inhibiting IL-6 receptors (IL-6Rs), tocilizumab (a humanized anti-IL-6R antibody) ameliorates the symptoms of these diseases and normalizes acute-phase proteins, including C-reactive protein (CRP). We found that tocilizumab treatment increased serum levels of IL-6 and soluble IL-6R (sIL-6R). To investigate the pathologic significance of these increases, we analyzed the kinetics of serum IL-6 and sIL-6R and the proportion of sIL-6R saturated with tocilizumab after tocilizumab administration in patients with RA and Castleman disease and then compared the results with the CRP values. Serum IL-6 and sIL-6R markedly increased after tocilizumab administration in both RA and Castleman disease. As long as free tocilizumab was detectable, sIL-6R was saturated with tocilizumab and IL-6 signaling was completely inhibited. We concluded that it is likely that sIL-6R increased because its elimination half-life was prolonged by the formation of tocilizumab/sIL-6R immune complex, and that free serum IL-6 increased because IL-6R-mediated consumption of IL-6 was inhibited by the unavailability of tocilizumab-free IL-6R. We also concluded that the increased level of free IL-6 during tocilizumab treatment closely reflects the actual endogenous IL-6 production and true disease activity.     

Changes of IL-6 and relevant cytokines in patients with hepatocellularcarcinoma and their clinical significance

AIM To study the changes of IL-6,IL-2, sIL-2R and TNF ir patients with hepatocellular carcinoma(HCC)and their clinical significance.METHODS IL-6, IL-2, sIL-2R and TNF were detected by avidin-biotin-system ELISA, double-sandwichELISA respectively in 60 patients with HCC and 36 patients with liver cirrhosis (LC) and 66 healthy persons.RESULTS The levels of IL-6, sIL-2R and TNF increased, but IL-2 level was lower in patients with HCCthan that in normal controls (NC) (t test, t=8.21, 4.71, 3.87, 2.13, P<0.01 or 0.05). IL-6 level in HCCwas 10 fold higher than NC, and also much higher than LC. IL-6 level was higher in later stage than that inearlier stage. There was a positive correlation between IL-6 and sIL-2R, TNF, while no positive correlationwas found between IL-2 and IL-6, sIL-2R in HCC.CONCLUSION The remarkably higher level of IL-6 is helpful for the early diagnosis of HCC.     

老年肺癌患者IL-6、sIL-2R和T细胞亚群检测的临床意义

目的　探讨老年肺癌患者外周血 IL - 6、s IL- 2 R和 T细胞亚群活性的变化。方法　对老年肺癌患者化疗前、后及老年健康对照组应用流式细胞分析法测定 T细胞亚群 ,双抗体夹心法 (EL ISA)测定 IL - 6及 s IL- 2 R水平。结果　肺癌组 s IL - 2 R、IL- 6及 CD8高于对照组 (P<0 .0 5) ,而CD3 及 CD4水平低于对照组 ,化疗后 s IL - 2 R、IL- 6及 CD8水平明显下降 ,但仍高于对照组 ,CD3 及 CD4水平略升高 ,仍低于对照组。结论　 IL - 6、s IL-2 R及 T细胞亚群联合测定可以反映肺癌病人机体免疫功能状态 ,可作为判断疾病的预后和免疫调节治疗的客观指标。     

白细胞介素-5、可溶性白细胞介素-2受体及一氧化氮与哮喘发病的关系

目的探讨白细胞介素-5(IL-5)、可溶性白细胞介素-2受体(sIL-2R)、一氧化氮(N())及嗜酸性粒细胞(EOS)在哮喘发病中的意义。方法对治疗前后的急性发作期、稳定期哮喘组及对照组血清II-5、sIL-2R和NO水平及EOS计数进行了研究。结果哮喘急性发作组血清IL-5、sIL-2R、NO及EOS水平均明显高于哮喘缓解期组与对照组。哮喘发作期IL-5与EOS呈显著正相关。哮喘急性发作期组治疗后sIL-2R及NO水平较治疗前显著降低，IL-5与EOS水平下降但无统计学意义。结论血清IL-5、sIL-2R、NO及EOS水平升高，与哮喘发作密切相关。     

Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis

Our objective was to evaluate the levels of interleukin-6 (IL-6), soluble receptors of IL-2 (sIL-2R), IL-10, and IL-1 receptor antagonists (IL-1ra) in the serum of patients with psoriatic arthritis (PsA) and to assess the correlation between these levels and parameters of clinical activity of skin and joint disease. In total, 34 patients with PsA and ten healthy volunteers participated in the study. Assessment of joint disease included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory spinal back pain, and Schober test. Current severity of skin disease was graded according to the psoriasis area and severity index (PASI). Erythrocyte sedimentation rate (ESR) was determined as a marker of disease activity. Serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were measured by an enzyme immunoassay kit. Significantly higher serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were found in patients with PsA in comparison with healthy volunteers. A statistically significant correlation was found between levels of sIL-2R and PASI, whereas no association was found with clinical parameters of joint severity. Levels of IL-1ra correlated with the number of tender and swollen joints. No correlation was found between levels of IL-6, IL-10, and clinical parameters of skin and joint severity. In the group of patients with PsA, serum levels of sIL-2R clearly correlated with severity of skin disease, whereas levels of IL-1ra were associated with joint severity. Received: 18 June 1999 / Accepted: 1 October 1999     

Treatment with fluvastatin rapidly modulates, via different pathways, and in dependence on the baseline level, inflammation in hemodialysis patients

BACKGROUND: Hemodialysis (HD) patients are frequently in an elevated inflammatory state which is correlated to the atherosclerosis-related and overall morbidity and mortality in this population. Statins, beyond their antilipidemic effects, are also considered to have anti-inflammatory, immunomodulating and antioxidant properties. The individual response of HD patients to a short course of fluvastatin, the mechanisms involved in the immunomodulating and anti-inflammatory effects of this drug and the time interval to the appearance of these effects are investigated in this longitudinal study. METHODS: In a group of 51 HD patients, fluvastatin 40 mg/day was administered for 4 weeks. Serial measurements of the lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin-10 (IL-10), and serum oxidized LDL (ox-LDL), were performed before, during, and after the treatment period. RESULTS: Total cholesterol was significantly reduced after 14 days of treatment with fluvastatin (from mean +/- SD 216.7 +/- 34.3 to 179.2 +/- 42.3 mg/dl, p < 0.001). IL-6 and ox-LDL were reduced on day 28 (p < 0.001 and p < 0.01, respectively) and IL-10 was increased on day 14 (p = 0.05); CRP did not change significantly during the treatment period while sIL-6R was increased on day 28 of fluvastatin administration (p < 0.05). In a subgroup of patients with CRP, IL-6, sIL-6R, and ox-LDL baseline serum values > or = the median and IL-10 < or = the median, CRP was reduced on day 28 of fluvastatin treatment (p < 0.01), IL-6 and ox-LDL were reduced earlier, on day 14 (p = 0.05 and p < 0.05, respectively) while sIL-6R did not change significantly during the treatment period. CONCLUSIONS: Treatment with fluvastatin rapidly modulates inflammation in HD patients. Enhancement of anti-inflammatory mechanisms and attenuation of the inflammatory and oxidative state contribute to this modulation. Patients in an elevated baseline inflammatory state respond more rapidly and effectively to the treatment. This immediate and multi-potent action of the statins could be clinically useful in acute atherosclerosis complications or in the treatment of chronic inflammation in HD patients.     

狼疮性肾炎患者血清IL-6和sIL-2R水平变化的检测

目的探讨狼疮性肾炎(LN)患者血清中白细胞介素(IL)-6和可溶性IL-2受体(sIL-2R)的水平变化及临床意义。方法利用酶联免疫吸附试验(ELISA)检测42例LN患者和40例正常健康人血清IL-6和sIL-2R的水平。结果活动期LN组患者IL-6和sIL-2R水平显著高于静止期LN组患者及正常对照组(P<0.01),静止期LN组患者IL-6和sIL-2R水平显著高于正常对照组,差异有显著性(P<0.01)。结论LN患者血清IL-6和sIL-2R显著升高,可能与LN的发生发展有关,并可作为病情及疗效判断的观察指标。     

The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab

BackgroundIL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses.MethodsHeparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients.ResultsThree statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90–183) pg/ml, in g2 12.3(4.4–24) pg/ml, and in g3 60.1(30–146) pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72 ng/ml, in g2 269.1 ± 125 ng/ml, and in g3 732.7 ± 243 ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5–15), g2 = 12(8–20), and g3 23(16–26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6 m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups.ConclusionsRA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.     

白血病患者脑脊液中可溶性白介素—2受体、白介素—6水平的测定及其临床意义

目的　探讨可溶性白介素 2受体 (sIL 2R)、白介素 6 (IL 6 )在急性淋巴细胞性白血病(ALL)的脑脊液 (CSF)中的表达及意义。方法　用双抗夹心ELISA法测定 30例ALL患者CSF中sIL 2R、IL 6水平 ,并与 10名正常者进行对照。结果　ALL合并中枢神经系统白血病 (CNS L)组较CNS L已缓解及未合并CNS L组二者水平显著升高 (P <0 .0 1) ;CNS L已缓解组二者水平接近对照组 (P >0 .0 5 ) ;骨髓缓解及好转组二者水平低于治疗无效组。结论　监测二者水平变化有助于CNS L早期诊断、评估疗效及预后。     

Clodronate treatment reduces serum levels of interleukin-6 soluble receptor in Paget's disease of bone

OBJECTIVE: Interleukin-6 (IL-6) and its soluble receptor (sIL-6R) stimulate osteoclast formation and activity. The primary cell abnormality in Paget's disease of bone (PDB) involves osteoclasts. Pagetic osteoclasts overproduce IL-6 and IL-6 receptor in vitro. In vivo, IL-6 serum levels are very high in the acute phase of PDB. The aim of this study was to evaluate the modification in the serum levels of IL-6, sIL-6R and osteotropic hormones (parathormone, 25OHD3 and 1,25(OH)2D3) as a in long-term response to clodronate treatment in patients with PDB. METHODS: 16 patients (8 females) with polyostotic PDB were studied. IL-6, sIL-6R and osteotropic hormones serum levels were evaluated in active PDB and after clodronate treatment (300 mg injected intravenously for 5 consecutive days). The sequential changes in total alkaline phosphatase (tALP) serum levels were used to assess the maximal pharmacological response to treatment. RESULTS: In untreated pagetic patients, mean serum levels of IL-6 (3.20+/-1.18 pg/ml) and sIL-6R (35.02+/-8.33 ng/ml) were significantly increased. Serum osteotropic hormone levels fell within the normal range. Eight weeks after treatment, the maximal pharmacological response to clodronate was associated with a significant reduction of sIL-6R serum levels in all patients, without a significant variation in serum IL-6 and osteotropic hormone levels. Moreover, we observed a correlation between lower sIL-6R serum levels before clodronate therapy and complete remission of PBD, defined as a decrease of tALP serum levels within the normal range. CONCLUSION: The decrease in serum sIL-6R levels could be one of the molecular mechanisms that play a role in the clinical response to clodronate treatment in PDB.