TNF-α和IL-6检测在急性冠脉综合征发病中的意义

目的　探讨急性冠脉综合征患者血清TNF -α和IL -6的浓度与发病的关系。方法　选择急性冠脉综合征 (急性心肌梗死及不稳定心绞痛 )患者 3 6例 ,其中急性心肌梗死 7例 ,不稳定心绞痛患者 2 9例。根据不稳定心绞痛患者病情的严重程度将其按Braunwald分级分为三组 :Ⅰ级 9例 ;Ⅱ级 8例 ;Ⅲ级 12例。采用放免法测定急性冠脉综合征患者血清TNF -α和IL -6的浓度。结果　不稳定心绞痛患者由Ⅰ级组到Ⅲ级组随病情加重IL -6的浓度是逐渐升高的(P <0 .0 5 ) ,但血清TNF -α无明显升高 ;急性心肌梗死患者血清IL -6浓度在心梗发作后 6小时和 48小时有两个高峰 ,血清TNF -α在心梗发作后 2 4小时达到高峰 ;IL -6和TNF -α与反映心肌损伤的酶CK -MB无直线相关性。结论　不稳定的心绞痛患者随着病情加重体内IL -6水平逐步升高 ;AMI患者发病过程中伴随IL -6和TNF -α的升高 ,但IL -6和TNF -α的动态曲线不同 ;IL -6和TNF -α浓度的升高与AMI的心肌损伤严重程度无关     

间断人工重力在模拟失重所致胸主动脉炎症反应中的对抗作用

目的 观察模拟失重大鼠胸主动脉炎症反应变化以及间断人工重力对抗模拟失重所致变化的作用.方法 采用尾部悬吊方法建立模拟失重大鼠模型,将45只雄性Sprague-Dawley大鼠随机分为3组,每组15只(n=15).即对照(CON)组、4周尾部悬吊(HU)组和1 h/d间断人工重力(IAG)组.建模成功后,分离大鼠胸主动脉...     

Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis

Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), thereby inducing proinflammatory cytokines such as IL-1β and tumor necrosis factor alpha (TNF-α). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1β and TNF-α significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-α) did not induce IL-32 expression in Huh-7.5. However, IFN-α exerted a significant additive effect on TNF-α-induced but not IL-1β-induced IL-32 expression, particularly in CD14+ monocytes. This effect was dependent both on NF-κB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays. CONCLUSION: IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli.     

老年慢性阻塞性肺病患者CRP、IL-1β、TNF-α水平的临床意义

目的探讨C反应蛋白（CRP）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）在老年慢性阻塞性肺病（COPD）的血清表达水平及临床意义。方法分别测定58例老年健康人群（对照组）,62例老年COPD急性加重期患者（AECO-PD组）和54例老年COPD稳定期患者（COPD稳定期组）血清CRP、IL-1β、TNF-α水平。结果对照组CRP、IL-1β、TNF-α的血清浓度值明显低于AECOPD组及COPD稳定期组,COPD稳定期组CRP、IL-1β、TNF-α的血清浓度值明显低于AECOPD组,两者之间的差异具有统计学意义（P〈0.01）。结论 CRP、TNF-α、IL-1β等细胞因子在COPD的发病及急性加重中起重要作用,而且与机体的系统性炎症反应有密切关系。     

Effect atorvastatin on serum tumor necrosis factor alpha and interleukin-1β following acute pulmonary embolism

This study was designed to investigate the effect of atorvastatin on the serum levels of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) following acute pulmonary embolism (PE). Forty New Zealand white rabbits were divided into control and atorvastatin groups. Acute PE was created by injection of autologous blood clots into the femoral vein. Enzyme-linked immunosorbent assay was used to measure TNF-α and IL-1β. At baseline, there was no significant difference in serum TNF-α (10.6 ± 1.3 versus 11.2 ± 1.9 pg/mL; P > .05) or IL-1β (8.2 ± 1.0 versus 8.6 ± 0.9 pg/mL; P > .05) between the control group and the atorvastatin group. In both groups, there was a significant increase in the serum TNF-α and IL-1β following acute PE. However, the levels of serum TNF-α and IL-1β in the atorvastatin group was significantly lower than in the control group following PE (P < .01). The authors conclude that acute PE is associated with a significant increase in serum proinflammatory factors TNF-α and IL-1β. Pretreatment with atorvastatin diminished the increase in TNF-α and IL-1β.     

不稳定性心绞痛患者介入治疗围术期CD4 T淋巴细胞磷酸酶基因表达的变化

目的探讨不稳定性心绞痛患者PCI围术期CD4T淋巴细胞张力蛋白同源第10染色体丢失的磷酸酶基因(PTEN)表达的变化。方法连续入选拟行择期PCI的不稳定性心绞痛患者42例,分别于PCI术前、术后16²4h抽取新鲜外周血20ml,免疫磁珠法分选出CD4T淋巴细胞,荧光定量PCR检测PTEN mRNA表达,蛋白免疫印迹法检测PTEN蛋白表达,酶联免疫吸附法检测TNF-α及白细胞介素10(IL-10)炎性相关因子的表达。结果与PCI术前比较,PCI术后患者肌钙蛋白I高于正常高值的发生率为45.4%;与PCI术前比较,PCI术后血浆TNF-α水平明显升高,PTEN mRNA、PTEN蛋白和IL-10明显下降,差异有统计学意义(P<0.05,P<0.01)。直线相关分析显示,PTEN蛋白与TNF-α呈负相关(r=-0.874,P<0.01),与IL-10呈正相关(r=0.732,P<0.05)。结论 PCI术可能通过下调PTEN的表达,促进相关炎性因子的分泌,从而诱发心肌炎症损伤。     

急性冠状动脉综合征患者血清炎性细胞因子水平及临床意义

目的通过对急性冠状动脉综合征患者血清炎性细胞因子水平的测定及比较,分析炎症及细胞因子在急性冠状动脉综合征发生发展过程中的作用及临床意义。方法选择急性心肌梗死(AMI)患者44例(AMI组),不稳定性心绞痛(UAP)患者44例(UAP组),稳定性心绞痛(SAP)患者43例(SAP组),无冠心病患者35例(对照组),分别检测各组患者血清白细胞介素6(IL-6)、白细胞介素8(IL-8)、白细胞介素10(IL-10)、TNF-α、C反应蛋白(CRP)和基质金属蛋白酶9(MMP-9)浓度并进行比较。结果 AMI组患者血清IL-6、IL-8、IL-10、TNF-α、CRP和MMP-9水平均明显高于SAP组和对照组(P<0.01);AMI组患者血清IL-10、TNF-α、CRP、MMP-9水平明显高于UAP组(P<0.05);UAP组患者血清IL-6、IL-8、IL-10水平明显高于SAP组和对照组;MMP-9和CRP与IL-6呈正相关(r=0.308,r=0.384,P<0.01)。结论冠心痛与炎性反应密切相关,多种细胞因子参与了动脉粥样硬化斑块的形成和进程,血清炎性细胞因子水平的升高是冠状动脉粥样硬化斑块不稳定的标志。     

Effect of Interleukin-1β and Tumor Necrosis Factor-α on the Expression of G-Proteins in CD4+ T-Cells of Atopic Asthmatic Subjects

Chronic use of β₂-agonists and increased production of inflammatory mediators during the late allergic reaction after the antigen challenge result in the desensitization of β-adrenoceptors in the airways with an accompanying rise in nonspecific airway hyperresponsiveness. Several proinflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), play a significant role in orchestrating and perpetuating the inflammatory response and induce the decreased response to bronchodilators in vitro. However, the underlying mechanisms are unknown. In this study, we examined the effect of two cytokines, IL-1β and TNF-α, on the expression of guanine nucleotide binding regulatory proteins (G-proteins), G_sα and G_iα-3, by Western blotting in the CD4⁺ cells of nonatopic nonasthmatic (NANA), atopic nonasthmatic (ANA), and atopic asthmatic (AA) subjects. In the purified CD4⁺ cells, the basal expression of G_sα was higher in the ANA group, and significantly lower in the AA group as compared to the NANA group. The basal expression of G_iα-3 was significantly greater (3–15 fold) than G_sα, with no significant difference between any of the three groups. Both cytokines IL-1β and TNF-α significantly decreased the expression of G_sα in the CD4⁺ cells of the NANA and ANA groups, with no effect in the AA group. However, these cytokines increased the expression of G_iα-3, proteins in the AA group, but had no effect in the CD4⁺ cells of the NANA and ANA groups. These data suggest that a decreased response to β₂-agonists in the late allergic response in allergic asthmatic subjects could be due to the release of inflammatory cytokines, which induce a decrease in the stimulatory G-proteins and an increase in the inhibitory G-proteins.     

前炎症细胞因子对人结肠腺癌细胞5-羟色胺转运体表达的影响

目的 研究前炎症细胞因子白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α对人结肠癌细胞(Caco-2细胞)5-羟色胺转运体(SERT)表达的影响.方法 Caco-2细胞系体外培养5d后,分为对照组(新鲜培养基)、IL-1β孵育组(50ng/ml)和TNF-α孵育组(50ng/ml),采用RT-PCR和Western印迹法分别观察各组2、24和48h时Caco-2细胞SERT mRNA的表达和24、48和72h时SERT蛋白的表达情况.结果对照组在2、24、48h时SERT mRNA相对表达水平分别为2.282±1.367、1.586±0.421和1.86±0.496;IL-1β孵育组分别为1.393±1.184、1.064±0.625和1.013±0.415,较对照组明显降低(P<0.05);TNF-α孵育组分别为1.000±0.000、0.829±0.162和0.945±0.147,较对照组明显降低(P<0.01),三组间比较差异有统计学意义(P<0.01).IL-1β孵育组和TNF-α孵育组于24、48、72h时SERT蛋白表达水平均低于对照组.结论 IL-1β和TNF-α在体外对结肠细胞SERT表达具有抑制作用,提示IL-1β和TNF-α可通过改变5-羟色胺系统的活性,影响内脏敏感性.     

溃疡性结肠炎患者肠道菌群变化与细胞因子、TLRs分子表达的相关性研究

目的探讨溃疡性结肠炎患者肠道菌群变化与细胞因子、TOLL样受体(Toll-like receptors,TLRs)分子表达的相关性。方法将2015年6月—2016年12月在山东省医学科学院第三附属医院确诊并接受治疗的溃疡性结肠炎患者78例作为试验组,同时选择未患溃疡性结肠炎的80例健康者作为对照组。分别对试验组和对照组进行肠道菌群检测,肠黏膜TLR2、TLR4、TLR5、TLR9分子表达检测和外周血IL-4、IL-6、IL-17、IL-23、TNF-α等炎性细胞因子表达检测,分析炎性细胞因子和TLRs表达与肠道菌群变化的关系。结果试验组双歧杆菌、乳杆菌含量明显低于对照组(P均0.05),拟杆菌、肠杆菌、肠球菌、梭杆菌含量明显高于对照组(P均0.05);试验组肠黏膜组织中TLR2、TLR4、TLR5、TLR9表达明显高于对照组(P均0.05);试验组外周血IL-4表达低于对照组,IL-6、IL-17、IL-23、TNF-α等炎性细胞因子表达高于对照组(P均0.05)。Pearson相关性分析显示,TLR2、TLR4、TLR5、TLR9表达与拟杆菌、肠杆菌、肠球菌含量呈正相关,与双歧杆菌、乳杆菌含量呈负相关;与IL-6、IL-17、IL-23、TNF-α表达呈正相关,与IL-4表达呈负相关。结论溃疡性结肠炎患者正常肠道菌群平衡被打破,促炎因子表达增加,抑炎因子表达减少,TLRs分子表达增加。肠道菌群紊乱可能通过增强TLRs分子表达来促进促炎因子的分泌,介导肠黏膜炎性反应。     

Peritoneal exudate cells from long-lived rats exhibit increased IL-10/IL-1β expression ratio and preserved NO/urea ratio following LPS-stimulation in vitro

In humans, usual aging, differently from successful aging, is associated with deregulation of proinflammatory/anti-inflammatory cytokine balance. The corresponding data from rat studies are limited. Therefore, we examined (i) cytokine messenger RNA (mRNA) profile of fresh peritoneal cells from 6- (adult), 24- (old), and 31-month-old (long-lived) AO rats and (ii) proinflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine, NO, and urea production in their LPS-stimulated cultures. Comparing with adult rats, cells from old ones expressed lower amount of TNF-α and IL-6 mRNAs, but greater amount of IL-1β mRNA. On the other hand, cells from long-lived rats exhibited a dramatic increase in IL-10 mRNA expression followed by diminished TNF-α and IL-6 mRNA expression, and comparable expression of IL-1β mRNA relative to adult rats. Consequently, IL-10/IL-1β mRNA ratio was greater in cells from long-lived rats than in adult and old rats. In LPS-stimulated peritoneal cell cultures (contained ≥95 % macrophages) from old rats, concentration of common proinflammatory cytokines was higher than in those from adult rats. Comparing with adult and old rats, in LPS-stimulated macrophage cultures from long-lived rats, TNF-α and IL-6 concentrations were lower; IL-1β concentration was comparable or greater (in respect to adult rats), whereas that of IL-10 was strikingly higher. Consistently, in macrophage cultures from long-lived rats, NO (iNOS activity marker)/urea (arginase activity marker) ratio was less and not different from that in old and adult rats, respectively. The study suggests that macrophages from long-lived rats, differently from those of old ones, have substantial ability to limit proinflammatory mediator production, which may contribute to their longevity.     

Increased levels of IL-6, IL-1β, and TNF-α in Kashin–Beck disease and rats induced by T-2 toxin and selenium deficiency

The objective of this study is to investigate the possible role of inflammatory mediators such as IL-6, IL-1β, and TNF-α in Kashin–Beck disease (KBD) children and rats fed with T-2 toxin under a selenium-deficient nutrition status in order to determine possible mechanism underlying KBD. Sprague–Dawley rats were administered a selenium-deficient diet for 4 weeks prior to their exposure to T-2 toxin for 4 weeks. The morphology of joint cartilages of KBD children and rats was examined by light microscopy, and the expression of proteoglycans was determined by histochemical staining. The serum levels of IL-6, IL-1β, and TNF-α were determined by enzyme-linked immunosorbent assay. IL-6, IL-1β and TNF-α were localized by immunohistochemistry, and their mRNA levels were detected by real-time RT-PCR. The serum levels of IL-6 were significantly elevated in rats fed with selenium-deficient, T-2 toxin, and T-2 toxin plus selenium-deficient diets compared to those in the normal diet, while the serum levels of IL-1β and TNF-α were significantly increased only in the T-2 toxin plus selenium-deficient diet group. IL-6, IL-1β and TNF-α protein and mRNA levels in cartilage were significantly higher in rats with diets of T-2 toxin and T-2 toxin plus selenium deficiency than in rats fed normal or selenium-deficient diet. While staining for the cytokines in cartilages of KBD children was significantly higher than that in controls. T-2 toxin under a selenium-deficient nutritional status induces increased levels of IL-6, IL-1β, and TNF-α in serum and cartilages, which may account for the pathological mechanism underlying the cartilage damage in KBD.     

Oxidative damage, pro-inflammatory cytokines, TGF-α and c-myc in chronic HCV-related hepatitis and cirrhosis

AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-relatecl hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc.METHODS: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-αand c-myc in liver specimens was detected by semiquantitative comparative RT-PCR.RESULTS: TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05).IL-1β was higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-α and staging (P=0.05) and between IL-1β levels and grading (P= 0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1. (P=0.03).Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04)and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype (P= 0.02).CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.     

美托洛尔对大鼠冠状动脉微栓塞心肌中炎性细胞因子表达及心功能的影响

目的探讨美托洛尔对大鼠冠状动脉微栓塞心肌组织中炎性细胞因子表达及心功能的影响。方法雄性SD大鼠162只,经左心室注射42μm微栓塞球,建立大鼠冠状动脉微栓塞模型,将存活的100只大鼠随机分为微栓塞组(CME组,50只)、关托洛尔组(CME-M组,50只),另以左心室注射等量生理盐水为假手术组(S组,50只),各组按注射后3、6、12、24 h、4周共5个时间点,每个时间点各10只,观察炎性细胞因子在心肌组织中表达水平及对心功能的影响。结果与S组比较,CME组在微栓塞后3、6、12、24 h时间点TNF-α、白细胞介素1β(IL-1β)、白细胞介素10(IL-10)的mRNA和蛋白表达水平显著升高(P<0.05),LVEF显著下降(P<0.05),4周两组比较,无统计学差异。与CMF组比较,CME-M组3、6、12、24 h时间点TNF-α、IL-1β的mRNA和蛋白表达水平显著降低(P<0.05),IL-10的mRNA和蛋白表达水平显著升高(P<0.05),4周两组比较,无统计学差异。与CME组比较,CME-M组12、24 h和4周LVEF显著升高(P<0.05)。结论美托洛尔可以明显改善冠状动脉微栓塞后心功能损伤,其作用机制可能与心肌炎性细胞因子表达有关。     

A shift in the balance of inhibitory and activating Fcgamma receptors on monocytes toward the inhibitory Fcgamma receptor IIb is associated with prevention of monocyte activation in rheumatoid arthritis

OBJECTIVE: To assess surface expression of the inhibitory receptor for IgG (Fcgamma receptor IIb [FcgammaRIIb]) in relation to activating FcgammaR on monocyte/macrophages from patients with rheumatoid arthritis (RA) and healthy controls and to study the influence of proinflammatory and antiinflammatory cytokines on the balance of inhibitory and activating FcgammaR. METHODS: Using a combination of genotyping and phenotyping, surface expression of FcgammaRIIb on monocytes from healthy control subjects and RA patients was demonstrated. Expression of FcgammaR on CD14+ monocytes was assessed by flow cytometry. Regulation of inhibitory and activating FcgammaR on monocytes by proinflammatory (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha]) and antiinflammatory (interleukin-4 [IL-4], IL-10) cytokines was studied. A functional change in cytokine-modulated monocytes was assessed in secondary cultures by their ability to produce TNFalpha upon FcgammaR crosslinking by IgG. RESULTS: Monocytes from healthy controls and RA patients expressed FcgammaRIIb at similar levels, in contrast to the higher levels of activating FcgammaRI and FcgammaRIIa in RA patients. The regulation of FcgammaR expression was comparable for patients and controls. IFNgamma selectively up-regulated FcgammaRI. TNFalpha down-regulated expression of FcgammaRIIb and the activating FcgammaR, whereas IL-10 up-regulated expression of monocytic FcgammaRIIb and all activating FcgammaR. Increased or sustained levels of activating over inhibitory FcgammaR induced by IFNgamma, TNFalpha, and IL-10 alone were associated with enhanced IgG-triggered TNFalpha production. In contrast, IL-4 and, more specifically, IL-4 plus IL-10 altered the FcgammaR balance in favor of FcgammaRIIb and completely prevented IgG-triggered TNFalpha production. CONCLUSION: The altered balance of FcgammaR in favor of activating receptors in RA may contribute to increased activation of monocyte/macrophages. A change in the FcgammaR balance toward the inhibitory FcgammaRIIb may offer a novel treatment strategy for preventing the pleiotropic activity of FcgammaR-triggered macrophages.     

Monocyte Activation in Platelet Concentrates

Background and Objectives: Cytokines in platelet concentrates contribute to febrile transfusion reactions. Activated monocytes are a major source of inflammatory cytokines, however the role of monocytes in cytokine production in platelet concentrates has not been clarified. This study undertook to quantitate monocytes, determine whether monocyte activation occurs and identify an association with IL-6 and IL-β concentrations in platelet concentrates. Materials and Methods: 17 platelet concentrates were analysed for total leucocyte and monocyte counts, CD14 and CD16 monocyte-associated antigen expression and IL-1β and IL-6 measurements on days 1, 2, 3, 4 and 5. Results: Monocytes in all platelet concentrates expressed increased levels of CD14 and CD16 from day 1 of storage. 10/17 platelet concentrates had elevated IL-6 levels by day 3. Platelet concentrates with IL-6 levels above 15 pg/ml on day 5 had monocyte counts between 0.14 and 15.6×10⁶/unit on day 1, while those with IL-6 levels below 15 pg/ml had low monocyte counts of <0.01 to 1.2×10⁶/unit on day 1. Conclusion: Monocytes present in platelet concentrates exhibit features of activation. Monocyte activation is present following the preparation of platelet concentrates, implicating the manufacturing process in its development. Increased IL-6 and IL-1β levels during platelet concentrate storage are commonly associated with a higher monocyte count. However, no direct association could be identified between the extent of monocyte activation and the level of cytokine release.