血浆D-二聚体、FDP、和尿ALB/Cr联合检测对早期糖尿病肾病临床诊断的价值

目的 探究血浆D-二聚体、FDP和尿ALB/Cr联合检测对早期糖尿病肾病临床诊断的价值.方法 选取我院2019年1月至2020年10月收治的113例早期糖尿病肾病患者作为EDN组,另选取50例单纯2型糖尿病患者作为T2DM组,并选取50例健康体检者作为健康对照组,检测三组受试者血浆D-二聚体、FDP的水平和尿ALB/Cr比值,并比较单个指标检测与联合检测对早期糖尿病肾病诊断的价值.结果 EDN组血浆D-二聚体和FDP均高于T2DM组和健康对照组,尿ALB/Cr比值低于T2DM组和健康对照组,差异有统计学意义(P<0.05),血浆D-二聚体、FDP和尿ALB/Cr联合检测诊断早期糖尿病肾病的特异性与灵敏度分别为95.38％和96.21％,较单个指标检测高.结论 血浆D-二聚体、FDP和尿ALB/Cr联合检测对早期糖尿病肾病的临床诊断具有一定的参考价值.     

2型糖尿病患者血IL-6与循环内皮细胞的关系及意义

目的探讨2型糖尿病(DM)患者血管内皮细胞损伤与血白介素6(IL-6)的关系及其意义。方法检测45例2型DM患者及20例正常人外周血IL-6和循环内皮细胞(CEC)水平并进行比较。结果①2型DM患者血IL-6和CEC水平高于正常人(P<0.05);②早期糖尿病肾病患者血CEC水平明显高于单纯糖尿病患者(P<0.01);③多元逐步回归分析显示CEC与血IL-6水平和尿蛋白排泄率(UAER)显著相关,标准偏回归系数β分别为0.264(P=0.033)和0.545(P=0.000)。结论2型糖尿病血管内皮细胞损伤与体内IL-6升高有密切关系,并在糖尿病肾病的发病过程中起一定作用。     

皮肤AGEs荧光检测对糖尿病肾病的临床意义

目的 探讨皮肤AGEs荧光检测对糖尿病肾病的早期诊断价值及与糖尿病肾病分期相关性的临床意义。方法 将我院住院的122例糖尿病患者按尿白蛋白/肌酐比值,眼底检查及CKD分期分为单纯糖尿病组（DM0组）42例、糖尿病肾病eGFR≥45 ml/（min·1.73 m2）组（DKD1组）49例和糖尿病肾病eGFR＜45 ml/（min/1.73·m2）组（DKD2组）31例,选取同期行肾穿刺肾功能正常的非糖尿病患者51例为对照组（NC组）,分别检测各组皮肤AGEs、血白蛋白、尿微量白蛋白等指标。结果 ①糖尿病患者的皮肤AGEs、SBP、SCr、TG、TC均高于对照组,ALB、HB低于对照组,差异均有统计学意义（P＜0.05）;②与DMO组比较,DKD1组和DKD2组的SBP、肌酐、UA、24hUP、尿微量白蛋白、皮肤AGEs水平均升高,且DKD2组高于DKD1组,差异有统计学意义（P＜0.05);而TP、ALB、HB水平均降低,且DKD2组低于DKD1组,差异有统计学意义（P＜0.05）;③糖尿病患者皮肤AGEs水平与尿微量白蛋白水平呈正相关（r=0.484,P＜0.05）。④皮肤AGEs是糖尿病肾病相关的危险因素[OR=1.113,95%CI（1.055,1.174）]。⑤ROC曲线分析显示皮肤AGEs检测糖尿病肾病的敏感性为68.75%,特异性为71.43%。结论 AGEs可能参与糖尿病肾病发生发展,荧光检测皮肤AGEs可用于早期筛查DKD并且评估其病变程度。     

糖尿病肾病患者血清IL-1、IL-6含量测定

目的：检测糖尿病肾病患者血清白介素-1、白介素-6的水平,为进一步探讨与糖尿病肾病的关系提供资料。方法：2型糖尿病69例,尿白蛋白排泄率（UAE）在20-200 μg/min的21例患者为DN₁组,UAE>200 μg/min 22例患者为DN₂组,UAE<20 μg/min的26例为DM组,正常对照组20例,用免疫放射法测定血清IL-1、IL-6水平。结果：DN₂组血清IL-1含量为(31.23±6.69) ng/L,高于正常对照组[(21.37±8.24) ng/L]及DM组[(26.45±7.19) ng/L)], P<0.01, P<0.05。DM组血清IL-6含量为(1.50±0.79) μg/L,明显高于对照组（P<0.01）,DN₁组含量(1.02±0.77) μg/L,DN₂组为(0.97±0.67) μg/L,均低于DM组（两者P<0.05）。结论：糖尿病合并肾病患者血清IL-1水平高于正常对照及DM组,血清IL-6低于DM组提示其与糖尿病肾病的发病可能有一定的关系。     

血、尿IL-6变化在糖尿病肾病中的意义

目的 探讨血、尿IL-6变化在糖尿病肾病诊断治疗中的意义.方法 将实验对象分为观察组和对照组,观察组52人,对照组40人.根据尿白蛋白排泄率(UAER)将观察组又分为两个小组:分别为微量蛋白尿组DN1(24例)和临床蛋白尿组DN2(28例).对照组选取40名健康成年人.观察各组血、尿IL-6水平.结果 ①观察组病人血、...     

丙型肝炎患者血清IL-6、IL-10与HA、PⅢP含量相关性的探讨

目的:探讨了白细胞介素IL-6、IL-10在丙型肝炎患者肝纤维化中的作用,为无创伤的血清学指标,对丙型肝炎患者提供新的肝纤维化指标。方法:分别应用ELISA法对92例丙型肝炎患者(其中轻度38例,中度31例,重度23例)进行IL-6、IL-10检测,放射免疫分析检测HA、PⅢP含量,并分析它们之间的关系。结果:丙型肝炎患者血清IL-6、IL-10、HA、PⅢP水平均非常显著地高于正常人组(P<0.01),相关分析表明,丙型肝炎患者血清HA、PⅢP水平与IL-6、IL-10浓度的相关系数(r)分别为0.6252(P<0.01)、-0.3124(P<0.05),0.2526(P<0.05),-0.2914(P<0.05)。结论:细胞因子IL-6、IL-10在肝纤维化形成中发挥重要作用,在早期肝纤维化的诊断中具有一定的临床实用价值。     

血清IL-6、IL-10、CRP和PCT水平检测对手足口病早期 合并细菌感染患儿的临床诊断价值

目的 探讨血清IL-6、IL-10、CRP和PCT水平检测对手足口病早期合并细菌感染患儿的临床诊断价值。方法 选取我院收治的早期手足口病患儿90例为观察组,并根据患儿是否合并细菌感染分为单纯组51例和感染组39例,选取同期来我院体检的健康儿童50例为对照组,比较三组间IL-6、IL-10、CRP和PCT水平差异。结果 观察组患儿IL-6、IL-10、CRP以及PCT水平高于对照组,差异有统计学意义（P＜0.05）;感染组患儿CRP以及PCT水平高于单纯组,差异具有统计学意义（P＜0.05）;感染组和单纯组IL-6、IL-10水平比较,差异无统计学意义（P＞0.05）。结论 IL-6、IL-10水平在鉴别手足口病是否合并细菌感染方面的意义有待于进一步研究,而联合CRP和PCT检测可为临床鉴别早期手足口患儿是否合并细菌感染提供可靠的实验室依据,利于临床早期用药治疗。     

NLR、CRP及IL-6、IL-17在子宫内膜异位症中的表达及与病情的相关性

目的探讨NLR(中性粒细胞与淋巴细胞比值)、CRP(C反应蛋白)、IL-6(白细胞介素6)、IL-17(白细胞介素17)在子宫内膜异位症(EMs)中的表达水平及其与病情的相关性。方法回顾性分析2017年7月至2019年7月在唐山市妇幼保健院妇科行腹腔镜手术的126例术后病理确诊为EMs的患者作为研究对象,其中Ⅰ~Ⅱ期为轻度组(73例),Ⅲ~Ⅳ期为重度组(53例),选取同期体检的健康妇女50例作为对照组。分别测定各组CRP、IL-6、IL-17及NLR指标的水平,分析各指标的关系并应用Logistic回归分析各指标与EMs严重程度的相关性。结果EMs组患者血清中的CRP、IL-6、IL-17和NLR水平均高于对照组,IL-6分别与IL-17和CRP成正相关(r=0.348,P<0.05;r=0.308,P<0.05),CRP与NLR成正相关(r=0.297,P<0.05)其他指标间无显著相关性。重度组CRP、IL-6、IL-17水平均高于轻度组,差异有统计学意义(P<0.05)NLR重度组与轻度组差异无统计学意义(P>0.05)。Logistic回归分析显示,CRP、IL-6、IL-17与EMs病情均密切相关(P<0.05),三者联合诊断EMs的价值最高。结论CRP、IL-6、IL-17和NLR参与了EMs的发生、发展,三个指标的检测可评估EMs的病情及预后判断,CRP、IL-6、IL-17三个指标联合检测可提高EMs诊断的灵敏度和特异性。     

PCT、IL-6 和 CRP 联合检测预测未足月胎膜早破患者新生儿早发性败血症的临床意义

目的:探讨联合检测降钙素原(procalcitonin,PCT)、白细胞介素-6(Interleukin-6,IL-6)和C反应蛋白(C-reactive protein,CRP)对未足月胎膜早破患者新生儿早发性败血症的预测价值.方法:对我院2013年2月至2020年2月的未足月胎膜早破患者进行研究,共计50例,设为观察组,另设同期50例产检正常者为健康对照组,另将观察组新生儿根据感染情况分成非感染组和早发性败血症组,对比PCT、IL-6和CRP单一检测和联合应用诊断价值,另对比两组产妇炎症因子水平和不同新生儿炎症因子水平.结果:联合疾病诊断敏感性、特异性、准确性、阳性预测值和阴性预测值高于单一指标,组间对比有统计学差异(P<0.05).观察组产妇PCT、IL-6和CRP水平高于对照组;早发性败血症组各项指标高于健康对照组和非感染组,存在统计学差异(P<0.05).结论:未足月胎膜早破患者PCT、IL-6和CRP水平都比较高,可通过检测新生儿脐血炎症因子水平,有助于早期诊断早发性败血症.     

老年糖尿病酮症酸中毒患者IL-6和氧化应激的变化

目的: 探讨老年糖尿病酮症酸中毒(DKA)患者白细胞介素6(IL-6)和氧化应激的变化.方法:检测老年糖尿病酮症酸中毒患者治疗前后血IL6、 8异前列腺素F-2α(8-isoprostaglandinF2α,8isoPGF2α)水平、超氧化物歧化酶(SOD）活性、总抗氧化能力(TAC)和丙二醛(MDA）含量.结果:在DKA患者SOD、 TAC显著低于对照组(P<0.05), 而IL6、 MDA和8isoPGF2α显著高于对照组(P<0.05); DKA患者治疗后的SOD和TAC显著高于治疗前患者(P<0.05), 而IL-6、 MDA和8isoPGF2α显著低于治疗前患者(P<0.05).DKA患者治疗前IL6与8isoPGF2α呈显著性正相关(r=0.33, P<0.05）, 治疗后IL-6与SOD呈显著性负相关(r=-0.36, P<0.05）.DKA患者治疗前后IL-6与MDA均呈显著性正相关(r=0.38, 0.41, P<0.05）.结论: DKA患者血清IL-6水平明显升高, 且与氧化应激有关.     

IL-6

In the late 1960s, the essential role of T-cells in antibody production was reported. This suggested to us that certain molecules should be released from T-cells for the stimulation of B-cells. We discovered activities in the culture supernatant of T-cells that induced proliferation and differentiation of B-cells. The factor that induced B-cells to produce immunoglobulins was named B-cell stimulatory factor (BSF)-2. The complementary DNA that encoded human BSF-2 was cloned in 1986. Simultaneously, interferon-β2 and 26-kDa protein in the fibroblasts were independently cloned by different groups and were found to be identical to BSF-2. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte-stimulating factor also were proven to be the same molecule as BSF-2. Various names were used for this molecule because of its multiple biological activities, and thereafter, these names were unified as interleukin (IL)-6. Since the discovery of IL-6, rapid progress has been made in understanding its actions, the IL-6 receptor system, and the IL-6 signal transduction mechanism. More importantly, it was involved in numerous diseases, such as rheumatoid arthritis and Castleman’s disease. By accumulating the basic knowledge, a new therapeutic approach by blocking IL-6 actions appeared to be feasible for chronic inflammatory diseases.     

Immunoadhesins of interleukin-6 and the IL-6/soluble IL-6R fusion protein hyper-IL-6

Signal transduction in response to interleukin-6 (IL-6) results from homodimerization of gp130. This dimerization occurs after binding of IL-6 to its surface receptor (IL-6R) and can also be triggered by the complex of soluble IL-6R and IL-6. We fused IL-6 to the constant region of a human IgG1 heavy chain (Fc). IL-6Fc was expressed in COS-7 cells and purified via Protein A Sepharose. Using three different assays we found that the biological activity of this dimeric IL-6 protein is comparable with monomeric IL-6. Recently, we described the designer cytokine Hyper-IL-6 (H-IL-6) in which soluble IL-6R and IL-6 are connected via a flexible peptide linker. This molecule turned out to be 100-1000 times more effective than unlinked IL-6 and soluble IL-6R. Hyper-IL-6 acts on cells only expressing gp130 and is a potent stimulator of in vitro expansion of early hematopoietic precursors. Here we show that a Fc fusion protein of H-IL-6 (H-IL-6Fc) has the same biological activity on BAF/gp130 cells as H-IL-6. Furthermore, both H-IL-6 forms have a similar ability to induce the synthesis of acute phase proteins in human hepatoma cells HepG2 and in mice in vivo. The introduction of a thrombin cleavage site between H-IL-6 and the Fc portion of H-IL-6Fc made it possible to specifically recover biologically active monomeric H-IL-6 by limited proteolysis of the fusion protein. A more general use of cleavable immunoadhesins expressed in mammalian cells is discussed.     

Anti-murine IL-6 receptor antibody inhibits IL-6 effects in vivo

Thrombopoiesis, as well as antibody production, is one of the major events in which interleukin-6 (IL-6) has been reported to be involved. Polyclonal anti-murine IL-6 receptor antibody was prepared to examine the effect of the antibody on these events in IL-6-treated mice. Administration of the anti-mIL-6R antibody inhibited the IL-6-induced increase in the number of platelets. Enhancement of the serum level of DNP-specific antibody by intraperitoneal injection of IL-6 was inhibited completely with simultaneous administration of the anti-mIL-6R antibody. The level of DNP-specific antibody was decreased, even below the basal value, by the higher dose of anti-mIL-6R antibody, indicating its effect also on endogenous IL-6. This work provides evidence that anti-IL-6R antibody inhibits IL-6 function in vivo, and provides an animal model of the therapeutic use of anti-IL-6R antibody for IL-6-related disease.     

Analysis of interleukin 6 (IL-6)/IL-6 receptor system using monoclonal anti-IL-6 antibodies.

To investigate the IL-6/IL-6 receptor system, we obtained five murine monoclonal antibodies against human IL-6, which neutralize its biological activity. We classified them into two groups (Type I mAb and Type II mAb) according to the epitopes they recognized. These two types of antibodies showed no difference in the manner in which they neutralized IL-6 activity, but they differed in the way they inhibited the binding of IL-6 to its receptor. While Type I mAb inhibited IL-6 binding to its receptor completely, Type II mAb inhibited only partially, even at a concn of Type II mAb sufficient to neutralize biological activity. Scatchard plot analysis revealed that in the case of the human myeloma cell line, the U266 cell, which showed two-phase binding of IL-6 to its receptor, the high affinity binding disappeared and the affinity of the low affinity binding decreased in the presence of Type II mAb. These results suggest that Type I mAb neutralizes IL-6 activity by the blocking of IL-6 binding to its receptor directly. In contrast, Type II mAb neutralizes IL-6 activity not by direct blocking of IL-6 binding to its receptor, but by modulating the binding affinity of IL-6 to its receptor, that is, inhibiting the formation of high affinity binding in IL-6 receptor system. This also indicates that the formation of high affinity may be necessary to transduce the IL-6 signal.     

Influence of interleukin-6 (IL-6) autoantibodies on IL-6 binding to cellular receptors

Neutralizing autoantibodies to interleukin-6 (aAb-IL-6) have been reported in healthy individuals, in patients with autoimmune diseases, and in pharmaceutically prepared pooled IgG (IVIg). We investigated the ability of aAb-IL-6 derived from IVIg to interfere with IL-6 binding to the undifferentiated monocytic cell line U-937. High-affinity aAb-IL-6, primarily of the IgG₁ subclass, constituted approximately 1:10⁶ of the total IgG in IVIg preparations. IL-6 binding to cellular receptors was strongly inhibited by one class of aAb-IL-6. These antibodies recognized epitope(s) on IL-6 essential for the binding of IL-6 to the α subunit of the IL-6 receptor (IL-6R). Another class of aAb-IL-6 recognized epitope(s) on IL-6, which is not essential for the binding to IL-6R but nevertheless important for the formation of high-affinity cellular IL-6 binding. These antibodies presumably interfered with the association of IL-6 receptor β chains (gp130) with IL-6/IL-6R complexes, implicating that small IL-6/aAb-IL-6 immune complexes bound saturably (low affinity/high capacity) to cellular IL-6 receptors. There was no detectable binding of IL-6 through aAb-IL-6 and Fc receptors on U-937, and IVIg had no direct IL-6 receptor antagonizing activity. Dissociation kinetics of IL-6/aAb-IL-6 complexes at 37 °C revealed that IL-6 was liberated from 75% of the aAb-IL-6 with a half-time (t/2) ≈ 4 h but bound almost irreversibly to the remaining aAb-IL-6 (t/2 > 20 h). Cellular IL-6 uptake and degradation was suppressed by aAb-IL-6. Taken together, the data suggest that loss of immunologic tolerance against IL-6 might be a novel physiological mechanism by which IL-6 activities are effectively attenuated. Finally, binding of IL-6 in complex with IgG1 aAb-IL-6 on cells expressing IL-6 receptors implicates that such cells could be targets of antibody-dependent immunological reactions, including cytotoxic reactions.     

IL-6-soluble IL-6 receptor complex inhibits the proliferation of dermal fibroblasts

A number of investigators has reported that there is increased production of interleukin-6 (IL-6) by fibroblasts and monocytes from the patients with systemic sclerosis (SS). However, the precise role of IL-6 in the pathogenesis of SS remains unclear. On the basis of our previous study showing that the complex of IL-6 and soluble IL-6 receptor (sIL-6R) could induce synovial fibroblast proliferation, we examined whether the IL-6-s1L-6R complex could induce the proliferation of normal dermal fibroblastic cells (DF). IL-6 suppressed DF proliferation, and, in the presence of sIL-6R, dose-dependently showed much stronger suppressive effects on DF proliferation. This suppression was completely blocked by either anti-IL-6 or anti-sIL-6R antibody. Furthermore, the IL-6-sIL-6R complex significantly suppressed IL-1β-, TNFα- and PDGF-AA-induced DF proliferation. These lines of evidence suggest that the IL-6-sIL-6R complex may have potential as a useful agent for the treatment of SS.     

采用IL－6cDNA控针检测人IL－6基因表达

采用缺口平移技术对ＩＬ—６ｃＤＮＡ进行了生物素和同位素标记，证明两种标记的ＩＬ－６ｃＤＮＡ（３０ｎｇ／ｍｌ）均可检出低至５ｐｇ的同源ＤＮＡ，而模拟探针（５００μｇ／ｍｌ）对高达１００ｎｇ的同源序列无此反应。应用ＩＬ－６ｃＤＮＡ对富含ＩＬ－６ｍＲＮＡ的标本进行斑点杂交或Ｎｏｒｔｈｅｒｎ杂交，证明人参三醇皂甙促进了淋巴细胞ＩＬ—６基因表达（４倍），人胎脾单个核细胞、人胎脑组织匀浆和人胎胰岛细胞内均含有高浓度ＩＬ—６ｍＲＮＡ。