急性高原肺水肿患者血清中VEGF,TNF-α,IL-6及NO的含量变化

目的：检测高原肺水肿患者发生及转归过程中内皮生长因子（VEGF）,肿瘤坏死因子-α（TNF-α）,白介素-6（IL-6）和一氧化氮（NO）的含量变化,探讨高原肺水肿发生发展可能的病理生理机制。方法：收集10例高原肺水肿患者治疗前和转归后的血清样本,采用酶联免疫法和硝酸还原测定VEGF,TNF-α,IL-6和NO的含量。结果：VEGF在高原肺水肿发病时血清的含量为（167.9±26.5）pg/ml,而转归之后其含量显著降低为（53.1±17.0）pg/ml,（P〈0.01）;TNF-α在血清中的含量从发病时的（86.2±24.1）pg/ml减少到转归后的（29.2±6.8）pg/ml,（P〈0.05）,有显著性差异。而IL-6的水平也从发病时的（32.3±16.5）pg/ml变化为转归后的（12.5±8.0）pg/ml,虽然有下降的趋势,但没有统计学差异。而高原肺水肿患者血清中的NO水平从发病时的（33.8±3.3）μmol/L明显的升高到转归后的（74.1±6.2）μmol/L,（P〈0.01）。结论：VEGF,TNF-α,IL-6和NO参与了高原肺水肿的发生和转归过程。     

NF-kappaB-dependent regulation of tumor necrosis factor-alpha gene expression by CpG-oligodeoxynucleotides

Immunostimulatory activities of synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODNs) have gained attention as potentially useful immunotherapeutics. However, CpG-ODNs induce harmful and lethal shock effects because they greatly enhance the sequence-dependent induction of tumor necrosis factor-alpha (TNF-alpha). We have shown that phosphorothioate-modified oligodeoxynucleotides (PS-ODNs) of the CpG-ODN 1826 stimulate TNF-alpha gene expression, TNF-alpha promoter activity, IkappaB degradation, and NF-kappaB activation at higher levels compared with its phosphodiester ODN (PO-ODN). In contrast to the effects of CpG-ODN 1826, PS-ODN of the CpG-ODN 2006 showed lower stimulatory activities than its PO-ODN. Using transient transfection, it was found that myeloid differentiation protein (MyD88) and tumor necrosis factor receptor-associated factor 6 are commonly required for activation of the TNF-alpha promoter by various CpG-ODNs with different potencies. These results strongly suggest a possibility to optimally activate the innate immune responses by modulating the potency of CpG-ODNs via sequence rearrangement and phosphorothioate backbone modification.     

Effects of tumor necrosis factor-alpha and interleukin-6 in elderly populations

Aging is associated with low-grade increases in circulating levels of TNF-alpha and IL-6. A wide range of factors, including smoking, obesity, infections, the decline in sex hormones, and the genotype, induce and modify this age-related inflammatory activity, which on the other hand may cause age-related pathology. Several classical risk factors are indeed controlled by TNF-alpha and IL-6. TNF-alpha induces insulin resistance and endothelial dysfunction, IL-6 promotes procoagulant changes and both cytokines cause dyslipidaemia. Moreover, systemic low-grade elevations in both cytokines have been related to cardiovascular diseases and TNF-alpha has been associated with Alzheimer's disease and type 2 diabetes mellitus. TNF-alpha and IL-6 are also differently and independently of each other associated with mortality in elderly populations, indicating points of distinction in the biological effects of the two cytokines. Moreover, the association between cytokines and mortality is independent of co-morbidity, suggesting that low-grade increases in circulating cytokines are strong, independent risk factors of morbidity and mortality in old populations, although life style factors and co-morbidity may modulate levels.     

血清细胞因子变化在新生儿感染性肺炎中的诊断价值

研究IL-6、TNF-α和IL-2R在肺部感染性肺炎新生儿中的诊断价值。

收集2018年12月至2020年12月在本院妇产科出生新生儿(胎龄34~42周)资料, 根据肺部超声结果, 将新生儿分为病例组和正常组, 检测脐血中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-2受体(IL-2R), 独立样本t检验分析差异性, 多元线性回归分析IL-6、TNF-α及IL-2R与出现肺部感染的相关性, ROC曲线分析IL-6、TNF-α及IL-2R的灵敏度, VITEK-60系统鉴定病原菌。

两组一般资料剖宫产率、性别、出生体质量、胎龄等差异均无统计学意义(P > 0.05);与正常组比较, 病例组脐血炎性标志物IL-6、TNF-a、IL-2R水平均升高(P < 0.01);多元线性回归分析IL-6、TNF-a、IL-2R与新生儿出现肺部感染有关(P < 0.05);ROC曲线分析IL-6(> 155.270 pg/mL)的灵敏度为98.5%, 特异性为85.0%, 约登指数max=0.808;TNF-α(> 16.795 pg/mL)的灵敏度为89.6%, 特异性为86.7%, 约登指数max=0.763;IL-2R(> 603.935 U/mL)的灵敏度为70.8%, 特异性为86.7%, 约登指数max=0.575;病例组检出病原菌143株, 包括127例革兰阴性杆菌(肺炎克雷伯菌构成比最高, 为25.87%)和16例革兰阳性杆菌(表皮葡萄球菌构成比最高, 为2.80%)。

IL-6、TNF-α和IL-2R对肺部感染性肺炎具有识别作用, 在鉴别和预测新生儿出现感染性肺炎具有诊断价值。

     

Effects of heavy resistance training on maximal and explosive force production, endurance and serum hormones in adolescent handball players

To determine the effects of 6-weeks of heavy-resistance training on physical fitness and serum hormone status in adolescents (range 14-16 years old) 19 male handball players were divided into two different groups: a handball training group (NST, n = 10), and a handball and heavy-resistance strength training group (ST, n = 9). A third group of 4 handball goalkeepers of similar age served as a control group (C, n = 4). After the 6-week training period, the ST group showed an improvement in maximal dynamic strength of the leg extensors (12.2%; P < 0.01) and the upper extremity muscles (23%; P < 0.01), while no changes were observed in the NST and C groups. Similar differences were observed in the maximal isometric unilateral leg extension forces. The height of the vertical jump increased in the NST group from 29.5 (SD 4) cm to 31.4 (SD 5) cm (P < 0.05) while no changes were observed in the ST and C groups. A significant increase was observed in the ST group in the velocity of the throwing test [from 71.7 (SD 7) km x h(-1) to 74.0 (SD 7) km x h(-1); P < 0.001] during the 6-week period while no changes were observed in the NST and C groups. During a submaximal endurance test running at 11 km x h(-1), a significant decrease in blood lactate concentration occurred in the NST group [from 3.3 (SD 0.9) mmol x l(-1) to 2.4 (SD 0.8) mmol x l(-1); P < 0.01] during the experiment, while no change was observed in the ST or C groups. Finally, a significant increase (P < 0.01) was noted in the testosterone:cortisol ratio in the C group, while the increase in the NST group approached statistical significance (P < 0.08) and no changes in this ratio occurred in the ST group. The present findings suggested that the addition of 6-weeks of heavy resistance training to the handball training resulted in gains in maximal strength and throwing velocity but it compromised gains in leg explosive force production and endurance running. The tendency for a compromised testosterone:cortisol ratio observed in the ST group could have been associated with a state of overreaching or overtraining.     

A meta-analysis of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in preeclampsia

Inflammation may play a major role in the pathogenesis of preeclampsia (PE). In this meta-analysis, we determined whether maternal polymorphisms and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were associated with PE. All studies investigating the associations between PE and maternal polymorphisms of TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G or serum concentrations of TNF-α, IL-6, and IL-10 were reviewed. We found that neither maternal TNF-α-308G/A (p=0.86, odds ratio [OR]=0.98, 95% confidence interval [CI], 0.76-1.25), IL-6 174G/C (p=0.14, OR=1.23, 95% CI, 0.93-1.61), nor IL-10-1082A/G (p=0.72, OR=1.07, 95% CI, 0.75-1.52) were associated with PE. On the other hand, maternal TNF-α (p<0.00001, weighted mean difference [WMD]=19.63 pg/ml, 95% CI, 18.54-20.72 pg/ml), IL-6 (p<0.00001, WMD=6.58 pg/ml, 95% CI, 5.49-7.67 pg/ml), and IL-10 (p=0.0005, WMD=19.30 pg/ml, 95% CI, 8.42-30.17 pg/ml) concentrations were significantly higher in PE patients versus controls. Our findings strengthen the clinical evidence that PE is accompanied by exaggerated inflammatory responses, but do not support TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G as candidate susceptibility loci in PE.     

LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-alpha in human adipocytes

Adipose tissue-derived cytokines are presumably involved in obesity-associated pathologies including type 2 diabetes and atherosclerosis. Here we studied the lipopolysaccharide (LPS)-induced expression dynamics of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and IL-10 in human adipose tissue biopsies, in preadipocyte-derived adipocytes, and in mesenchymal stem cell (MSC)-derived adipocytes. TNFalpha, IL-6, IL-8 and IL-10 secretions by adipose tissue explants were increased 5.5-, 19.5-, 3.5- and 12.5-fold, respectively, by LPS (1 microg/mL) administration. Concordantly, IL-6 and IL-8 release was dose-dependently induced in MSC-derived adipocytes by LPS (>10 pg/mL). In contrast, TNFalpha and IL-10 remained undetectable even at the highest LPS dose (1 microg/mL) after 24h. In MSC- and preadipocyte-derived adipocytes, respectively, exposure to LPS evoked a weak and transient induction of TNFalpha mRNA whereas induction of IL-6 and IL-8 mRNA were pronounced and sustained for at least 24h. Basal glucose uptake, lipolysis and IL-6 mRNA were induced by exogenous TNFalpha (10 ng/mL) but not by IL-6 (10 ng/mL), IL-8 (100 ng/mL) and IL-10 (20 ng/mL). In this adipocyte model TNFalpha induces well known metabolic effects, but together with previous reports these data suggest that inflammation-induced TNFalpha may derive from non-adipocyte sources in adipose tissue, likely to be macrophages.     

腹腔镜与开腹手术对胃癌根治术患者TNF-alpha和IL-6 水平的影响研究

目的:探讨腹腔镜与开腹手术对胃癌根治术患者肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平的影响.方法:选取自2011年3月至2013年5月期间来我院就医并行胃癌根治术的72例胃癌患者作为研究对象.并将所有患者随机平均分成腹腔镜组和传统开腹组各36例.其中,腹腔镜组行腹腔镜辅助下胃癌根治术,传统开腹组行传统开腹胃癌根治术.比较两组手术时间、术中出血量、肛门排气时间及住院时间;比较两组患者术前及术后血清TNF-α和IL-6水平.结果:腹腔镜组术中出血量、肛门排气时间及住院时间均明显低于对照组(P＜0.05)腹腔镜组术后TNF-α和IL-6水平明显低于开腹组(P＜0.05),两组比较有显著性差异(P＜0.05).结论:腹腔镜辅助下胃癌根治术较传统开腹胃癌根治术术后血清TNF-α和IL-6水平低,对机体免疫功能影响较小,可减少患者术后感染机会,值得在临床中推广应用.     

The effects of peritoneal dialysis and hemodialysis on serum tumor necrosis factor-alpha, interleukin-6, interleukin-10 and C-reactive-protein levels

BACKGROUND: Markers of an acute phase reaction, such as C-reactive protein (CRP) or tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, are predictive for cardiovascular morbidity and mortality in normal subjects and in chronic renal failure patients. In this study, we aimed to investigate serum TNF-alpha, IL-6, IL-10 and CRP levels in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients. MATERIALS AND METHODS: Serum levels of TNF-alpha, IL-6, IL-10 and CRP levels were measured in 30 patients who were just diagnosed with end-stage renal failure and treated, with 16 CAPD (nine female, seven male) and 14 HD (eight female, six male) patients, before CAPD or HD treatment and after 3 months from the beginning of CAPD or HD in patients with no clinical signs of infection. The control groups were 20 healthy persons of similar age and sex. Serum levels of TNF-alpha, IL-6, IL-10 and CRP were measured by enzyme-linked immunosorbent assay in stable CAPD and HD patients and in healthy persons. RESULTS: The mean serum levels of TNF-alpha, IL-6, IL-10 and CRP showed no significant differences between the CAPD and HD patients for the beginning values and the third month of treatment. However, serum TNF-alpha, IL-6, IL-10 and CRP levels were higher than the control group in the CAPD and HD patients regarding the beginning values and the third month of treatment (p < 0.001). CONCLUSIONS: CAPD and HD of the renal replacement therapy have no effects on serum CRP and cytokines.     

Mechanisms of tumor necrosis factor-alpha and interleukin-6 induction during human liver transplantation

In human orthotopic liver transplantation (LTX) intraoperative elevations of TNF-alpha (> 100 pg/ml) and IL-6 (>800 pg/ml) have been found to correlate with early post-operative rejections and infections respectively. In this study the possible mechanism responsible for the induction of these cytokines has been investigated during liver allografting in 38 recipients. Intraoperative elevations of TNF-alpha (> 100 pg/ml) were detected in the majority of pre-transplant endotoxin positive recipients (8/12, > 10 endotoxin units/ml), the patients turning endotoxin positive until the end of grafting (3/5), and in a subgroup (6/21 patients), apparently endotoxin negative for the whole operation. Therefore endotoxin (ET) seems to stimulate release of TNF-alpha in approximately 50% of the patients, whereas sensitized Kupffer graft cells or immediate allograft reactivity of the host are likely to account for the remaining TNF-alpha positive cases. Elevations of IL-6 > 800 pg/ml) were found in approximately 50% of the TNF-alpha positive cases, indicating partially independent regulatory pathways for IL-6 induction in the TNF-alpha negative patients. In agreement with a previous study, 11/13 (85%) of the intraoperative TNF-alpha positive recipients rejected their grafts within the first 10 days post-operatively. These data demonstrate that ET/infection associated as well as ET independent/reperfusion associated intraoperative TNF-alpha elevations, promote the initiation of allograft rejection in human liver transplantation. The transient and low endotoxaemia caused by the liver grafting procedure performed without veno-venous bypass seems to be of minor importance in the intraoperative induction of TNF-alpha.     

多发性骨髓瘤与白细胞介素-6

白细胞介素-6是多发性骨髓瘤(multiple myeloma,MM)瘤细胞生长和生存的关键因子,也是MM患者发病的主要因子。IL-6/IL-6R系统通过不同通路影响多发性骨髓瘤瘤细胞生长并导致患者骨损害、类风湿性关节炎等一系列并发症。针对IL-6/IL-6R系统的治疗方法将给MM的治疗带来重大的进展。     

Cytokines and serum amyloid A in the pathogenesis of hepatitis C virus infection

Expression of the acute phase protein serum amyloid A (SAA) is dependent on the release of the pro-inflammatory cytokines IL-1, IL-6 and TNF-α during infection and inflammation. Hepatitis C virus (HCV) upregulates SAA-inducing cytokines. In line with this, a segment of chronically infected individuals display increased circulating levels of SAA. SAA has even been proposed to be a potential biomarker to evaluate treatment efficiency and the course of disease. SAA possesses antiviral activity against HCV via direct interaction with the viral particle, but might also divert infectivity through its function as an apolipoprotein. On the other hand, SAA shares inflammatory and angiogenic activity with chemotactic cytokines by activating the G protein-coupled receptor, formyl peptide receptor 2. These latter properties might promote chronic inflammation and hepatic injury. Indeed, up to 80 % of infected individuals develop chronic disease because they cannot completely clear the infection, due to diversion of the immune response. In this review, we summarize the interconnection between SAA and cytokines in the context of HCV infection and highlight the dual role SAA could play in this disease. Nevertheless, more research is needed to establish whether the balance between those opposing activities can be tilted in favor of the host defense.     

运动干预对衰老模型大鼠血清炎性因子水平的影响

目的:探讨6周跑台运动对D-半乳糖致衰老模型大鼠血清炎性因子水平的影响,以此阐明运动延缓衰老的部分机制。方法:将雄性SD大鼠随机分为正常对照组(NC组)、衰老对照组(AC组)、衰老训练组(AE组),每组8只。AC和AE组大鼠每日腹腔注射1次D-半乳糖125 mg/kg,NC组注射等量生理盐水,持续6周。同时,AE组进行6周中小强度跑台训练。6周后,各组大鼠腹主动脉取血,分离血清检测血清中白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的含量。结果:与正常对照组比较,衰老模型组大鼠血清IL-6、TNF-α水平明显升高(P＜0.01);与衰老模型组比较,衰老训练组大鼠血清IL-6、IL-10和TNF-α水平明显减少(P＜0.01),表明6周中小强度跑台训练有助于降低衰老机体促炎症因子的分泌,减弱体内炎症反应。结论:6周中小强度跑台训练在一定程度上可以纠正衰老机体内的炎性因子网络紊乱状况,起到干预炎性衰老的目的。     

Prostaglandin F2alpha amplifies tumor necrosis factor-alpha promoter activity by the FPB prostanoid receptor

This study examines the regulation of tumor necrosis factor-alpha (TNF-alpha) promoter activity by prostaglandin F2alpha ( PGF2alpha ) in HEK cells stably expressing either the FPA or FPB prostanoid receptors. Cells were transiently transfected with a luciferase reporter plasmid under the control of a TNF-alpha promoter and luciferase activity was measured. In the absence of PGF2alpha basal TNF-alpha reporter gene activity is elevated in FPB cells as compared with FPA cells. This elevated basal activity is blocked by pretreatment with a Rho inhibitor, but not by pretreatment with an inhibitor of protein kinase C (PKC). TNF-alpha reporter activity in FPB cells is stimulated by PGF2alpha and this is decreased by pretreatment with a chelator of intracellular calcium or by a gap junction inhibitor. In FPB cells pretreatment with a Rho inhibitor combined with either a calcium chelator or a gap junction inhibitor decreases both basal and PGF2alpha stimulated TNF-alpha reporter activity. Interestingly post-treatment of FPB cells with an inhibitor of PKC decreased PGF2alpha stimulated TNF-alpha reporter gene activity even though pretreatment did not. It, therefore, appears that PGF2alpha stimulated TNF-alpha reporter activity in FPB cells is amplified by a Rho-dependent mechanism involving calcium, gap junctions, and PKC. These findings may help in understanding the function of the FPB isoform in the corpus luteum.     

Jumping ability is related to change of direction ability in elite handball players

PurposeThis study investigated the relationship between vertical and horizontal jumping ability and change of direction (COD) to measure athletic performance in 51 elite male handball players.Scope.Countermovement jump (CMJ), peak power, and standing long jump (SLJ) were measured. Participants performed a 20-m sprint test (time measured at 5, 10, and 20 m) and a zigzag test (COD: 135°, 90°, and 45°). The COD deficit, an index of the time required for COD, was calculated. The correlations between CMJ height and zigzag test times were relatively large (at 135°, r =  − 0.607; at 90°, r =  − 0.594; at 45°, r =  − 0.613; p < 0.01), whereas those between CMJ height and COD deficit were moderate (at 135°, r =  − 0.399, p < 0.01; at 90°, r =  − 0.350, p < 0.05; at 45°, r =  − 0.323, p < 0.05). SLJ showed a negative moderate correlation with COD deficit (at 135°, r =  − 0.439, p < 0.01; at 90°, r =  − 0.469, p < 0.01; at 45°, r =  − 0.380, p < 0.01).ConclusionsThis study is the first to analyse SLJ ability and COD deficit parameters of handball players. We found that SLJ ability is moderately related to COD time and deficit; therefore, SLJ measurement may be a useful predictor of athletic performance.     

Insulin stimulates interleukin-6 and tumor necrosis factor-alpha gene expression in human subcutaneous adipose tissue

High circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are found in patients with hyperinsulinemia. Insulin stimulates release of IL-6 from adipocyte cultures, and it stimulates IL-6 gene expression in insulin-resistant, but not control, rat skeletal muscle. In addition, TNF-alpha may be involved in the pathogenesis of insulin resistance. Therefore, we studied the effect of insulin on IL-6 and TNF-alpha gene expression in human skeletal muscle and adipose tissue. Nine healthy young volunteers participated in the study. They underwent a 6-h hyperinsulinemic euglycemic clamp at a fixed insulin infusion rate, with blood glucose clamped at fasting level. Blood samples drawn at 0, 1, 2, 3, 4, 5, and 6 h were analyzed for IL-6 and TNF-alpha. Muscle and fat biopsies, obtained at 0, 2, 4, and 6 h, were analyzed for IL-6 and TNF-alpha mRNA with real-time PCR. IL-6 mRNA increased 11-, 3-, and 5-fold at 2, 4, and 6 h, respectively, in adipose tissue (ANOVA P = 0.027), whereas there was no significant effect of insulin on skeletal muscles. Plasma IL-6 increased during insulin stimulation. TNF-alpha mRNA increased 2.4-, 1.4-, and 2.2-fold in adipose tissue (ANOVA P = 0.001) and decreased 0.74-, 0.64-, and 0.68-fold in muscle tissue (ANOVA P = 0.04). Plasma levels of TNF-alpha were constant. In conclusion, the finding that insulin stimulates IL-6 and TNF-alpha gene expression in adipose tissue only and inhibits the TNF-alpha production in skeletal muscles suggests a differential regulation of muscle- and adipose tissue-derived IL-6 and TNF-alpha.