白细胞介素-6在肝再生中的作用

白细胞介素-6(IL-6)是一种多功能的细胞因子。近年来发现,它是启动肝细胞增殖的早期信号中不可缺少的组成部分,在肝再生中有重要作用。现对IL-6在肝再生中的作用及可能机制进行综述,为肝脏疾病的治疗提供新的思路。     

白细胞介素-8基因-251A/T多态性与急性胰腺炎的相关性研究

目的:探讨白细胞介素-8(Interleukin-8,IL-8)基因-251A/T位点单核苷酸多态性(Single nucleotide polymorphism,SNP)与急性胰腺炎的关系.方法:应用聚合酶链反应.限制性酶切片段长度多态性技术检测120例急性胰腺炎(Acute pancreatitis,AP)患者和132例健康对照组的IL-8-251A/T基因型分布情况.结果:病例组和对照组均检测到IL-8基因-251A/T位点AA、AT和TT3种基因型:IL-8基因-251A/T的基因型分布在AP组和对照组差另q有统计学意义(P＜0.05),AP组等位基因A频率明显增高(24.2%→34.2%);在轻型组和重型组差别有统计学意义(P＜0.05),重型组等位基因A频率明显增高(24.2%→42%);在重型合并Ⅰ型和Ⅱ型及SIRS组和非SIRS组各基因型比较差别无统计学意义(P＞0.05).结论:IL-8基因-25lA/T基因多态性可能是急性胰腺炎病情进展的危险因素.     

IL-6、IL-10联合BISAP评分在重症急性胰腺炎预后评估中的作用研究

目的:探讨白细胞介素-6(IL-6)、白细胞介素-10(IL-10)联合急性胰腺炎严重程度床边指数(BISAP)评分在重症急性胰腺炎(SAP)预后评估中的作用。方法:回顾性分析2013年5月至2016年5月我院收治的131例SAP患者的临床病历资料,患者入院后24h内采用酶联免疫吸附法(ELISA)检测血清IL-6和IL-10水平,并进行BISAP评分,同时以接近IL-6、IL-10、BISAP评分中位数的自然值为界值,比较不同预后(死亡、感染、多器官功能障碍综合征(MODS)、局部并发症)的发生率。结果:死亡、MODS、感染患者血清IL-6水平、BISAP评分高于局部并发症患者,血清IL-10水平低于局部并发症患者(P0.05);死亡、MODS患者血清IL-6水平、BISAP评分高于感染患者,血清IL-10水平低于感染患者(P0.05);死亡患者血清IL-6水平、BISAP评分高于MODS患者,血清IL-10水平低于MODS患者,差异有统计学意义(P0.05)。IL-6≥65μg/L、IL-1040μg/L、BISAP评分≥3分患者死亡、MODS、感染发生率更高,差异有统计学意义(P0.05)。经Pearson积矩相关分析,IL-6、BISAP评分之间呈正相关关系(r=0.617,P0.05),IL-6、BISAP评分与IL-10之间呈负相关关系(r=-0.572、-0.611,P0.05)。结论:IL-6、IL-10、BISAP评分是评估SAP预后的重要指标,IL-6水平、BISAP评分越高、IL-10水平越低,患者预后越差,联合应用的预测价值高,临床可作为参考。     

白细胞介素-6在骨骼肌质量调节中的作用

白细胞介素-6 (interleukin-6,IL-6)是一种多效性细胞因子参与机体免疫应答，并在不同器官、组织及细胞中发挥生物调节作用。IL-6具有抗炎和促炎的双重效应，在受到病原体感染发病的初期，机体内IL-6发挥抗炎作用，其水平在机体内适度升高，抵御机体炎症、维持机体内部稳态；但IL-6大量释放可造成过度炎症，引发机体的其他病理变化。而IL-6在调控骨骼肌质量方面亦有刺激骨骼肌蛋白质合成与降解的双重效应。骨骼肌作为机体重要的运动及代谢器官，也是IL-6的关键靶向之一。一方面，IL-6在应激骨骼肌的诱导和瞬时表达通过自分泌或旁分泌作用下，参与调节肌卫星细胞增殖、分化，介导骨骼肌生成与生长；另一方面，在衰老及病理条件下，机体IL-6水平显著提高，促使肌肉萎缩，因此，骨骼肌萎缩机制亦与IL-6相关。此外，骨骼肌也可作为内分泌器官，在运动应激下分泌并释放IL-6,后者作为“运动因子”实现骨骼肌与其他器官或组织间的“crosstalk”。鉴于IL-6在机体发挥的“多面手”作用，本文综述IL-6与骨骼肌质量调控机制相关研究进展，为揭示骨骼肌应激与适应分子机制提供理论参考。     

白细胞介素6构象研究进展

简要介绍了人白细胞介素6(hIL-6)的一级结构和高级结构;通过对hIL-6突变体的研究,发现hIL-6分子上存在2个活性位点(位点Ⅰ和位点Ⅱ),其中位点Ⅰ识别hIL-6受体(hIL-6R)的分子量为80×10~3的配基结合亚单位,位点Ⅱ与gp130结合参与信号转导,这使得合理设计hIL-6拮抗剂成为可能。     

白细胞介素-18及其抗肿瘤作用研究进展

白细胞介素18(IL-18)具有多向免疫调节功能。它对T细胞向Th1或Th2分化起有独特的调节能力。最近的研究表明了IL-18的结构、活化形式和调节树突状细胞、NK细胞等方面的重要功能。研究也发现许多肿瘤患者血清IL-18水平显著升高及其在肿瘤发生发展中的作用。本文主要介绍了IL-18的结构、产生与调节、生物学作用及其在肿瘤方面的研究进展。     

白细胞介素-6在酒精性肝病中的作用

酒精性肝病(alcoholic liver disease,ALD)是由于长期过量饮酒导致肝的内部组织发生炎症损伤的慢性肝病.乙醇及其衍生物在代谢过程中直接或间接诱导引起的肝炎症反应可能是ALD发病的重要机制.然而,该过程内在的细胞分子机制尚不明确.最新研究发现,白细胞介素-6(interleukin-6,IL-6)对...     

用一个简单快速的RT-PCR技术筛选白细胞介素-6作用相关基因

为了研究白细胞介素-6(IL-6)作用相关基因以及一些可能受IL-6调控的基因,利用一个简单快速的以PCR为基础的方案,检测了IL-6处理和未处理的Sko007细胞中基因表达的差异,克隆并鉴定了差异表达基因的cDNA片段.首先用6-mer寡核苷酸引物进行反转录从而最大限度地将mRNA编码区序列生成cDNA;然后用2或3个较长的随机引物进行PCR扩增,并以不同引物组合重复PCR增扩;扩增产物在2%琼脂糖凝胶上电泳分离,回收差异片段并直接用于克隆、测序及进一步分析.在此研究中,获得了3个表达序列标签(EST),其中一个为新的基因片段,反向RNA杂交有力证实了它们与IL-6作用的相关性.进一步的生物信息学分析表明,新基因片段STRF17在多种组织中表达.     

白细胞介素-10、白细胞介素-6对慢性肺源性心脏病预后评价的临床意义

目的:检测慢性肺源性心脏病患者血清白细胞介素-10和白细胞介素-6的水平,探讨细胞因子对慢性肺源性心脏病患者预后评价的临床意义。方法:将我院住院治疗的慢性肺源性心脏病患者40例,按照心功能情况分为肺源性心脏病组21例(对照组)和肺源性心脏病合并心力衰竭组19例(观察组),进行血清白介素-6、白介素-10定量检测。结果:观察组血清白介素-6水平较对照组明显升高,而白细胞介素-10却明显低于对照组(P值均<0.05)。结论:检测白细胞介素-6、白细胞介素-10的水平,可作为监测肺源性心脏病心功能恶化的预测指标。     

清胰汤对大鼠急性坏死性胰腺炎IL-6,IL-10 及肠道通透性影响

目的:探讨清胰汤改善大鼠急性坏死性胰腺炎(acute necrotizing pancreatitis)ANP炎症反应及肠道通透性功能的治疗效果及机制。方法:将72只雄性SD大鼠随机分为3组,其中2组大鼠采用从胰腺被膜下多点缓慢均匀注入3.8%牛黄胆酸钠(0.5ml/100g)建立大鼠急性坏死性胰腺炎模型,再分为急性坏死性胰腺炎常规治疗组(A组)、清胰汤干预治疗组(B组),其他24只大鼠为假手术组(S组),每组再随机分为24h、48h、72h组。各组于12h后给于肠内营养,B组肠内营养后给于2次清胰汤2.5ml/100g,A组、S组给于同等剂量生理盐水。各组于建模后24h、48h、72h处死,腹腔动脉取血检测血清淀粉酶浓度、IL-6、IL-10、D-乳酸水平。结果:48h时点B组IL-10水平较A组高(P<0.05);72时点B组血清淀粉酶水平较A组低(P<0.01),IL-6水平较A组低(P<0.01),IL-10水平较A组高(P<0.01),D-乳酸水平较A组低(P<0.01)。结论:清胰汤可以上调IL-10改善大鼠急性胰腺炎炎症反应从而降低肠道通透性。     

清胰汤对大鼠急性坏死性胰腺炎IL-6,IL-10及肠道通透性影响

目的：探讨清胰汤改善大鼠急性坏死性胰腺炎（acute necrotizing pancreatitis）ANP炎症反应及肠道通透性功能的治疗效果及机制。方法：将72只雄性SD大鼠随机分为3组,其中2组大鼠采用从胰腺被膜下多点缓慢均匀注入3.8%牛黄胆酸钠（0.5ml/100g）建立大鼠急性坏死性胰腺炎模型,再分为急性坏死性胰腺炎常规治疗组（A组）、清胰汤干预治疗组（B组）,其他24只大鼠为假手术组（S组）,每组再随机分为24h、48h、72h组。各组于12h后给于肠内营养,B组肠内营养后给于2次清胰汤2.5ml/100g,A组、S组给于同等剂量生理盐水。各组于建模后24h、48h、72h处死,腹腔动脉取血检测血清淀粉酶浓度、IL-6、IL-10、D-乳酸水平。结果：48h时点B组IL-10水平较A组高（P〈0.05）;72时点B组血清淀粉酶水平较A组低（P〈0.01）,IL-6水平较A组低（P〈0.01）,IL-10水平较A组高（P〈0.01）,D-乳酸水平较A组低（P〈0.01）。结论：清胰汤可以上调IL-10改善大鼠急性胰腺炎炎症反应从而降低肠道通透性。     

Interleukin-6 is a better marker of lethality than tumor necrosis factor in endotoxin treated mice

Abstract We established a mouse model to differentiate between a lethal and non-lethal presentation of endotoxic shock. The model involved injecting different amounts of Escherichia coli LPS into C3H/HeN mice which had been 'primed' with BCG. We found that the mice receiving non-lethal and lethal doses of LPS could not be differentiated in terms of their physical symptoms for the first 8 h post-injection. Tumour necrosis factor (TNF) was detected at concentrations 2–9-fold greater in mice receiving lethal doses of LPA when compared with non-lethally injected mice. However, given that (i) the successful detection of this differential was dependent on the time of sampling and (ii) that TNF was only detected in the first 3–4 h post LPS challenge, we suggest that TNF may not be very useful as a prognostic marker in endotoxic shock. In contrast, circulating IL-6 appeared to mirror the symptoms of the endotoxic mice. The relative disappearance of IL-6 after 10 h in the non-lethally injected mice corresponded with their symptomatic recovery, while IL-6 continued to circulate up to the time of death in the lethally injected mice. Furthermore, there appeared to be a good correlation between the levels of injected LPS and the levels of IL-6 induced into the circulation. Our results suggest that IL-6, rather than TNF, may serve as a prognostic marker for endotoxic shock.     

Lipopolysaccharide-Enhanced Expression of Interleukin-6 in Dibutyryl Cyclic AMP-Differentiated Rat C6 Glioma

Abstract: Rat C6 glioma synthesizes a low basal level of interleukin-6 (IL-6). Stimulation with 10 µg/ml of lipopolysaccharide (LPS) and induction of differentiation with 1 m M N ⁶, O ^2'-dibutyryl cyclic AMP (dbcAMP) for 48 h increased the secreted activity to 400 and 800 U/ml, respectively. An LPS stimulation of dbcAMP-differentiated cells strongly enhanced the secreted activity. Depending on the dbcAMP concentration, the cell number, and the stimulation time, the secreted IL-6 level increased up to 120,000 U/ml. After 48 h of costimulation with 10 µg/ml of LPS and 1 m M dbcAMP, northern blotting and immunoassay demonstrated an eightfold increase in IL-6 mRNA concentration and IL-6 immunoreactivity, whereas titration of the biological activity indicated a 100-fold increase in the secreted IL-6 activity. The enhanced secretion of IL-6 is correlated with the induction of differentiation. Chromatography on heparin-Sepharose and on DEAE-5PW separated the secreted activity into several fractions, indicating that they differ in heparin affinity and charge either by posttranslational modifications or by binding to a carrier protein. Each of the partially purified IL-6-like activities could be neutralized by an anti-murine IL-6 antibody. Our observations demonstrate that in vivo inflammatory signals can trigger astrocytes and their precursors to secrete substantially different levels of immunoregulatory cytokines depending on their degree of differentiation.     

Molecular Mechanisms of Actions of Interleukin-6 on the Brain,with Special Reference to Serotonin and the Hypothalamo-Pituitary-Adrenocortical Axis

Biological activities of the multifunctional cytokine, interleukin-6 (IL-6) include stimulation of B cell proliferation, immunoglobulin production, and initiation of the acute-phase response. IL-6 affects the CNS in that it activates the hypothalamo-pituitary-adrenocortical (HPA) axis and increases brain tryptophan and serotonin metabolism. IL-6 has been proposed as an important mediator of interaction between the neuroendocrine and immune systems. The peripheral and central effects of IL-6 are presumably mediated through its membrane receptor (IL-6R). IL-6, IL-6R and their respective mRNAs have been detected in several brain regions. Although the functions of cytokines overlap considerably, each displays its own characteristic properties. Expression of IL-6 in the brain has been observed in several CNS disorders, some of which have been associated with disorders of serotonin metabolism. It is proposed that interactions between IL-6 and brain serotonin is a complex process which involves corticotropin-releasing factor (CRF) and opioid peptides. It is likely that the molecular mechanisms underlying the actions of IL-6 on the HPA axis and its other brain functions involve the integrated effects of glutamate, Ca²⁺, 3,5-cyclic AMP, protein kinase C, and other metabolic pathways.     

乌司他丁治疗急性胰腺炎的临床疗效及机制研究

目的:探讨乌司他丁对急性胰腺炎患者的临床疗效及可能机制。方法:收集我院收治的重症急性胰腺炎患者66例,随机分为实验组和对照组。所有患者均给予禁食水、充分补液、纠正电解质紊乱等常规支持对症治疗。对照组予奥曲肽,实验组予乌司他丁,共治疗7天。测定两组患者治疗前、后各血清白介素-6(IL-6)、白介素-8(IL-8)及肿瘤坏死因子-α(TNF-α)水平;治疗前、治疗第1、3天及治疗后进行血常规检测,观察白细胞计数(WBC),并进行血淀粉酶(AMS)、尿淀粉酶(UAMY)测定;分别记录两组患者临床症状及体征恢复时间,判定临床疗效。结果:1治疗后,两组患者血清IL-6、IL-8及TNF-α水平均较治疗前显著下降,且实验组较对照组下降更明显(P0.05);2治疗后,两组患者白细胞计数及血、尿淀粉酶水平均较治疗前明显下降,且实验组较对照组下降更明显(P0.05);3治疗后,实验组各项临床症状及体征消失时间均明显短于对照组(P0.05)。结论:乌司他丁可有效改善急性胰腺胰腺炎患者的各项临床症状,这可能与其显著降低其血清IL-6、IL-8、TNF-α、淀粉酶水平、白细胞计数及尿淀粉酶水平有关。     

急性淋巴细胞白血病患儿血清25羟维生素D3、乳酸脱氢酶、白细胞介素-6水平与危险度分层和预后不良的关系研究

摘要 目的：探讨急性淋巴细胞白血病（ALL）患儿血清25羟维生素D3（25-OH-D3）、乳酸脱氢酶（LDH）、白细胞介素-6（IL-6）水平与危险度分层和预后不良的关系。方法：选择2018年6月至2019年8月在我院住院治疗的ALL患儿60例为病例组,另选取同期到我院健康查体的同龄健康儿童60例为对照组。采用酶联免疫吸附试验（ELISA）检测血清25-OH-D3和IL-6水平,采用全自动生化分析仪检测血清LDH水平,对比病例组与对照组血清25-OH-D3、LDH、IL-6水平,对比不同危险度分层ALL患儿血清25-OH-D3、LDH、IL-6水平,分析其与危险度分层的相关性。ALL患儿进行规范化治疗,根据治疗结果分为预后良好组和预后不良组,对比预后良好组和预后不良组临床特征及血清25-OH-D3、LDH、IL-6水平,采用COX比例风险回归模型分析预后不良的危险因素。结果：病例组患儿血清25-OH-D3水平低于对照组,血清LDH、IL-6水平高于对照组（P＜0.05）。低危型、中危型ALL患儿血清25-OH-D3水平高于高危型,且低危型高于中危型（P＜0.05）;低危型、中危型ALL患儿血清LDH、IL-6水平低于高危型,且低危型低于中危型（P＜0.05）。预后不良组高危型患儿及白细胞计数＞100×10⁹/L的患儿所占比例、血清LDH及IL-6水平高于预后良好组（P＜0.05）,血清25-OH-D3水平低于预后良好组（P＜0.05）。血清25-OH-D3水平与ALL患儿危险度分层呈负相关（P＜0.05）,血清LDH、IL-6水平与ALL患儿危险度分层呈正相关（P＜0.05）。危险度分层及血清25-OH-D3、LDH、IL-6是ALL患儿预后不良的危险因素（P＜0.05）。结论：ALL患儿血清25-OH-D3、LDH、IL-6水平异常改变,与危险度分层相关,是预后不良的危险因素。     

Pancreatic stellate cell-potentiated insulin secretion from Min6 cells is independent of interleukin 6-mediated pathway

Pancreatic stellate cells (PSCs) secrete various factors, which can influence the β-cell function. The identification of stellate cell infiltration into the islets in pancreatic diseases suggests possible existence of cross-talk between these cells. To elucidate the influence of PSCs on β-cell function, mouse PSCs were cocultured with Min6 cells using the Transwell inserts. Glucose-stimulated insulin secretion from Min6 cells in response to PSCs was quantified by enzyme-linked immunosorbent assay and insulin gene expression was measured by quantitative polymerase chain reaction. Upon cytometric identification of IL6 in PSC culture supernatants, Min6 cells were cultured with IL6 to assess its influence on the insulin secretion and gene expression. PLC-IP₃ pathway inhibitors were added in the cocultures, to determine the influence of PSC-secreted IL6 on Glucose-stimulated insulin secretion from Min6 cells. Increased insulin secretion with a concomitant decrease in total insulin content was noticed in PSC-cocultured Min6 cells. Although increased GSIS was noted from IL6-treated Min6 cells, no change in the total insulin content was noted. Coculture of Min6 cells with PSCs or their exposure to IL6 did not alter either the expression of β-cell-specific genes or that of miRNA-375. PSC-cocultured Min6 cells, in the presence of PLC-IP₃ pathway inhibitors (U73122, Neomycin, and Xestospongin C), did not revoke the observed increase in GSIS. In conclusion, the obtained results indicate that augmented insulin secretion from Min6 cells in response to PSC secretions is independent of IL6-mediated PLC-IP₃ pathway.     

Interleukin-6 and procalcitonin in children with sepsis and septic shock

Objectives. To examine the behavior of interleukin-6 (IL-6) and procalcitonin (PCT) and verify whether they can be used to differentiate children with septic conditions. Methods. Septic children aged between 28 days and 14 years, prospectively enrolled from 01/2004 to 12/2005, were divided into sepsis (SG; n = 47) and septic shock (SSG; n = 43) groups. IL-6 and PCT were measured at admission (T0) and 12 h later (T12h). PCT results were classed as: 0.5 ng/mL = sepsis unlikely; 0.5 to <2 = sepsis possible; 2 to <10 = systemic inflammation; 10 = septic shock. Results. Ninety children were included. At T0, there was a higher frequency of SSG with higher PCT compared with SG [SSG: 30 (69.7%) > SG: 14 (29.8%); p < 0.05]. Similar results were observed at T12h. PRISM was significantly higher for SSG patients with higher PCT than SG patients. At T0, IL-6 levels were higher in SSG [SSG: 213.10 (10.85–396.70) > SG: 63.21 (0.86–409.82); p = 0.001], but not statistically different at T12h. IL-6 levels positively correlated with PRISM score in SSG patients at admission (p = 0.001; r = 0.86). Conclusion. PCT and IL-6 appear to be helpful in early assessment of pediatric sepsis, are of diagnostic value at admission, and are related to disease severity.