充血性心力衰竭患者血浆TNF-α、IL-1β 和IL-6含量变化

目的检测充血性心力衰竭(CHF)患者血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)水平,了解这些细胞因子在CHF过程中的可能作用。方法取20例正常人和20例Ⅱ°-Ⅲ°CHF患者静脉血,用ELISA法测血清TNF-α、IL-1β和IL-6含量。结果CHF组这些细胞因子水平均明显高于对照组(P＜0.01);CHF程度越重,这些细胞因子浓度越高;TNF-α与IL-1β和IL-6含量之间呈正相关(r=0.9684,0.9768;P均＜0.01)。结论细胞因子TNF-α、IL-1β和IL-6可能参与CHF过程。     

流式微球阵列法检测肺结核患者血清部分细胞因子的临床意义

目的:探讨流式微球阵列法(CBA)检测不同类型肺结核患者血清中细胞因子IL-2、IL-4、IL-6、IL-10、TNF-α和IFN-γ水平的临床意义。方法:采用BD CBA Flex Set检测试剂盒和流式微球阵列法(CBA)检测84例肺结核患者(46例活动性肺结核患者及38例非活动性肺结核患者)和30例正常人的6种细胞因子(IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ)的水平。结果:肺结核患者血清IL-2、IL-6、IL-10和IFN-γ的水平显著高于正常对照组(P<0.01或P<0.05),且活动性结核组高于非活动性结核组(P<0.01或P<0.05)。血清IL-4与TNF-α水平肺结核患者与正常对照组无显著性差异。结论:CBA法能快速、灵敏、多参数批量同步定量检测血清中6种细胞因子;这些细胞因子在肺结核的免疫发病中具有重要的意义。     

老年抑郁症患者治疗前后血清细胞因子水平的研究

目的观测老年抑郁症患者使用盐酸帕罗西汀治疗前后血清细胞因子水平的变化。方法采用酶联免疫吸附法(ELISA)检测30例首发老年抑郁症患者(研究组)治疗前后的血清IL-6、IL-1β、TNF-α的水平并和30例健康老年人(对照组)比较,结合汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)总分及各因子分进行相关分析。结果研究组治疗前血清IL-6(63.24±15.67ng/1)、IL-1β(33.24±17.27ng/1)、TNF-α(29.24±15.67ng/1)水平显著高于对照组IL-6(31.41±11.51ng/l)、IL-1β(18.36±8.17ng/l)、TNF-α(18.24±10.56ng/l);P0.05。帕罗西汀治疗后血清IL-6、IL-1β、TNF-α水平较治疗前显著下降(P0.05)。结论血清IL-6、IL-1β、TNF-α水平升高可能是老年抑郁症的免疫学标志之一;帕罗西汀抗抑郁的同时降低血清IL-6、IL-1β、TNF-α水平。     

稳恒磁场刺激对糖尿病动脉粥样硬化大鼠血清和主动脉中VEGF、TGF-β1、TNF-α和IL-6表达的影响

目的:明确中等强度(4.0 m T)稳恒磁场刺激对糖尿病动脉粥样硬化大鼠血清和主动脉中的血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)表达的影响。方法:12周龄雄性SD大鼠30只,随机等分成3组(空白对照组、糖尿病组及糖尿病磁场暴露组)。对糖尿病和糖尿病磁场暴露组的大鼠采用链脲佐菌素+维生素D3+高脂饮食组合法建立糖尿病性动脉粥样硬化模型。糖尿病磁场暴露组接受强度4.0 m T全身稳恒磁场暴露,每天刺激2 h。8周后,全部大鼠处死,提取血清样本,进行血脂4项(血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇及低密度脂蛋白胆固醇)检测,并使用ELISA法检测血液中VEGF、TGF-β1、TNF-α和IL-6的蛋白表达;提取主动脉组织,使用PCR法检测主动脉中VEGF、TGF-β1、TNF-α和IL-6的基因表达。结果:稳恒磁场抑制糖尿病动脉粥样硬化大鼠血脂4项指标的升高(P0.05),同时显著降低血清VEGF、TGF-β1、TNF-α和IL-6表达(P0.05);PCR结果揭示稳恒磁场下调主动脉中VEGF、TGF-β1、TNF-α和IL-6基因表达(P0.05)。结论:中强度稳恒磁场对糖尿病性动脉粥样硬化的积极治疗效果可能与其对重要细胞因子(如VEGF、TGF-β1、TNF-α和IL-6)的表达调控作用有关。     

NIV毒素和硒对软骨细胞IL-1β、TNF-α分泌的影响

目的:通过测定NIV毒素和硒作用下软骨细胞IL-1β、TNF-α含量的变化,从细胞因子角度探讨大骨节病发病机制。方法:在体外单层和立体培养的人胚软骨细胞中加入NIV毒素和硒,构建软骨损伤模型,收集软骨组织、细胞和细胞培养液,用光学显微镜观察体外构建组织的形态;用分光光度法测定软骨细胞DNA含量;用酶联免疫吸附方法(ELISA)检测细胞培养液中IL-1β、TNF-α的水平。结果:形态学观察发现NIV毒素能抑制软骨细胞生长,局部出现点片状坏死;毒素加硒后,上述损伤变化减弱。NIV毒素作用下软骨细胞DNA的合成受到抑制,但培养液中IL-1β、TNF-α含量显著升高,毒素加硒与毒素组变化趋势一致,但数值略下降。结论:NIV毒素能诱导软骨细胞IL-1β与TNF-α的分泌,这可能是造成软骨细胞损伤的原因之一。     

干眼症患者结膜上皮细胞和泪液中TNF-α、IL-1β的表达及意义

目的:探讨干眼症患者结膜上皮细胞和泪液中肿瘤坏死因子-α(TNF-α)和白细胞介素1β(IL-1β)的表达及临床意义。方法:选择确诊为干眼症患者120例(162眼)和正常人50例(85眼),采用ELISA法检测泪液中TNF-α、IL-1β的表达,并应用免疫组织化学方法检测结膜上皮细胞中TNF-α、IL-1β的表达。结果:干眼症组患者结膜上皮细胞中TNF-α、IL-1β的阳性表达率均明显高于对照组(P0.01),泪液中TNF-α、IL-1β的表达水平也明显高于对照组(P0.01);干眼症组患者结膜上皮细胞和泪液中TNF-α、IL-1β的表达与BUT、Schii1ner I试验均呈负相关,与角膜荧光素染色呈正相关。结论:TNF-α和IL-1β是干眼症发生的炎性介质,其表达水平变化反映了干眼症的进展过程。     

脑梗死患者炎性细胞因子变化与神经功能缺损的关系

目的:探讨脑梗死患者血清中炎性细胞因子水平与病情严重程度的关系.方法:收集2006-01/2008-12脑梗死患者82例为研究组, 80例同期门诊体检的健康人为对照组, 检测其外周血清中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和可溶性细胞间黏附分子1(sICAM-1)水平.结果:急性期、恢复期脑梗死患者血清IL-1β、 TNF-α及sICAM-1水平均较对照组显著增高(P ＜0.01或P＜0.05), 脑梗死组急性期较恢复期明显增高(P＜0.01);中度损伤组和重度损伤组患者血清IL-1β、 TNF-α及sICAM-1水平均较轻度损伤组显著增高(P＜0.01或P＜0.05), 重度损伤组患者TNF-α及sICAM-1水平较中度损伤组明显增高(P＜0.01);多元线性回归分析结果显示, IL-1β、 TNF-α及sICAM-1表达水平与脑梗死患者的神经功能缺损程度评分呈线性正相关, 标准回归系数依次为0.618、 0.613和0.606.结论:IL-1β、 TNF-α及sICAM-1互相作用参与了急性脑梗死的炎症反应和再灌流损伤.对它们的监测可为早期临床治疗及康复干预提供试验指标, 以便控制脑卒中的进展及复发.     

小儿肾病患者治疗前后血清IL-6、TNF-α和VEGF检测的临床意义

目的:探讨了小儿肾病患者治疗前后血清IL-6、TNF-α和VEGF水平的变化及意义.方法:分别应用放射免疫分析和酶联双抗体夹心法测定了34例小儿肾病患者血清IL-6、TNF-α和VEGF的含量,并与30名正常健康儿童作比较.结果:小儿肾病患者在治疗前血清IL-6、TNF-α和VEGF水平均非常显著地高于正常儿童组(P＜0.01),经治疗2个月后与正常儿童组比较仍有显著性差异(P＜0.05).结论:小儿肾病的发生、发展与血清IL-6、TNF-α和VEGF水平密切相关.     

再生障碍性贫血患者治疗前后血清IL-8、TNF-α和VEGF检测的临床评估

目的:探讨再生障碍性贫血患者治疗前后血清IL-8、TNF-α和VEGF水平的变化及临床意义.方法:应用放免法和酶联法对30例再生障碍性贫血患者进行了血清IL-8、TNF-α和VEGF检测,并与35例正常健康人作比较.结果:再生障碍性贫血患者在治疗前血清IL-8、TNF-α水平非常显著地高于正常人组(P<0.01),而V...     

风险产妇部分细胞因子血清水平分析

目的:分析临产风险孕妇细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)血清水平变化。方法:选择正常足月产妇40例(正常足月产妇组),风险产妇(包括早产、产后大出血和多胎妊娠)60例(风险产妇组),入院后于产前空腹采集静脉血;选择非孕健康妇女40例作为对照组。采用化学发光法检测各组血清IL-1β、IL-6、IL-8、IL-10和TNF-α水平,并统计分析各组各指标水平差异。结果:各组血清IL-1β和IL-8水平差异无统计学意义(P0.05)。风险产妇组IL-6水平显著高于正常足月产妇组和对照组(P0.01)。风险产妇组IL-10水平高于对照组(P0.01),但低于正常足月产妇组(P0.05)。风险产妇组与正常足月产妇组TNF-α水平差异无统计学意义(P0.05),但均高于对照组(P0.05)。结论:临产前检测细胞因子水平,对产妇风险评估有一定辅助参考价值。     

大骨节病患者血清促炎症细胞因子水平的检测

目的探讨前炎症细胞因子TNF、IL-1β和IL-6在大骨节病(KBD)发病机制中的作用。方法采集62例KBD患者和60例健康对照的血清标本,采用双抗体夹心ELISA法测定血清前炎症细胞因子TNF、IL-1β和IL-6的水平。结果KBD患者血清IL-1β和IL-6的水平分别为(238.4±698.5)ng/L和(164.4±661.4)ng/L,健康人分别为(74.5±130.0)ng/L和(52.2±154.6)ng/L,但它们之间差异均不显著(P>0.05)。然而,KBD患者血清TNF的水平[(109.2±145.3)ng/L]高于健康对照[(40.9±89.7)ng/L],差异非常显著(P<0.01)。患者血清TNF与IL-1β的水平及血清TNF与IL-6水平的相关性均不显著(r值分别为0.0387和0.2135,P>0.05)。血清IL-1β与IL-6的水平呈显著的正相关(r=0.3460,P<0.01)。结论血清前炎症细胞因子水平的升高,可能与大骨节病的发病有关。     

Cytokine levels in patients with brucellosis and their relations with the treatment

PURPOSE: To determine the serum levels of proinflammatory and some of the Th1/Th2 cytokines in brucellosis and their alterations with treatment and outcome. METHODS: Twenty-eight acute and seven subacute brucellosis patients diagnosed clinically were included in the study. Twenty healthy volunteers were also included. Brucella standard tube agglutination tests and blood culture were conducted on all subjects. Cytokine levels of pre- and post-treatment period serum samples were measured by ELISA. RESULTS: The mean serum levels of IL-6, IFN-gamma and TNF-alpha were significantly higher in brucellosis patients compared to the control group ( P < 0.05). No significant differences were found between patient and control groups in terms of IL-1beta , TGF-beta 1, IL-2, IL-4 and IL-8 levels. There was a positive correlation between IFN-gamma, TNF-alpha and IL-6 levels with CRP levels. IL-6, IFN-gamma and TNF-alpha levels measured after treatment were statistically significantly lower than pre-treatment values ( P < 0.001). No differences were found in the levels of these cytokines between acute and subacute patients' sera. IL-6, IFN-gamma and TNF-alpha levels were higher in acute or subacute brucellosis patients. CONCLUSIONS: Although the levels of the cytokines were decreased significantly with effective and adequate treatment these alterations did not correlate with the extent or activity of the disease.     

The effects of alendronate and calcitonin on cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study

The present study was designed to determine if levels of serum cytokines, such as interleukin (IL)-1beta, IL-2, IL-2r, IL-6, IL-6r, IL-8, IL-10, and TNF-alpha are different in osteoporotic and non-osteoporotic postmenopausal women, and to evaluate the effects of calcitonin and alendronate therapies over a six month period on serum cytokine levels in postmenopausal osteoporotic women. Serum levels of IL-2, TNF-alpha and IL-8 were found to be significantly higher (p < 0.05), and serum IL-10, and IL-6r significantly lower in the calcitonin (N=60) and the alendronate (N=60) treatment groups than in the control group (N=50) (p < 0.05). But, no significant difference was apparent between the calcitonin and alendronate treated groups before treatment. Statistically significant changes occurred in patients, with respect to the levels of serum IL-6r, and IL-8 after one month (p < 0.05), in IL-2r, IL-6r, IL-8, IL-10 after three months, and in IL-1beta, IL-6r, IL-8, IL-10 and TNF-alpha after six months of calcitonin therapy (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-8 and IL-10 after three months, and in TNF-alpha after six months in the calcitonin treated group and in the control group, whereas these parameters were significantly different at baseline. In the alendronate treated group, statistically significant changes occurred in the levels of serum IL-1alpha and IL-6 after three months, and in IL-1beta, IL-6, IL-6r and TNF-alpha after six months (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-10 after three months or in TNF-alpha after six months between the alendronate treatment group and the control group, whereas these parameters were significantly different at baseline. In conclusion, we suggest that; 1) not only IL-1, IL-6, TNF-alpha and IL-11 but also IL-2, IL-8 and IL-10 may have roles in the etiopathogenesis of osteoporosis, 2) calcitonin therapy have a more distinct influence on serum levels of some cytokines and have an earlier effect than alendronate therapy (especially upon IL-2r, IL-8, and IL-10). Nevertheless, further longitudinal studies are needed to identify the cytokines involved in the pathogenesis of postmenopausal osteoporosis and to evaluate the influence of different treatments on these cytokines.     

Immunological interactions in different forms of coronary heart disease

The study included measurement of serum levels of IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha, as well as the expression of mRNA IL-1beta, IL-2, IL-6, and TGfb1 in the vascular wall of patients with coronary atherosclerosis (angina, myocardial infarction). IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha serum levels in patients with coronary atherosclerosis were found to significantly higher than those in healthy individuals (control group). Detection of IL-1beta, IL-2, IL-6, and TGFb1 in tissues revealed mRNA of the cytokines under study in radial artery wall. The main aortic cytokine was found to be IL-2 (7 samples out of 8); the main cytokines in peripheral arteries were IL-1beta and IL-6 (5 samples out of 8). The results show that elevation of IL-1beta, IL-2, and IL-8 in patients with coronary atherosclerosis demonstrates an immunoinflammatory nature of the disease; the detection of dissimilar cytokines in tissue samples reflects not only different degree of vessel involvement, but also a phase character of the process.     

Passive dual immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta maximally ameliorates acute aminonucleoside nephrosis.

Rats receiving a single dose (10 mg/100 g) of aminonucleoside of puromycin (PAN) develop heavy proteinuria and acute interstitial nephritis (AIN). Whole isolated glomeruli from rats injected with PAN secreted both TNF-alpha and IL-1 beta cytokines. TNF-alpha secretion was first and maximally detected on day 3, whereas IL-beta activity was found on day 7, when rats were heavily proteinuric and AIN developed. In vivo treatment with either anti-TNF-alpha or anti-IL-1 beta antibodies produced a drastic and simultaneous reduction in both levels of proteinuria and intensity of interstitial cell infiltrate. These effects improved when both antibodies were administered together. Our studies demonstrate the effectiveness of immunosuppressive therapy against these two cytokines in rats with PAN-induced nephrosis.     

Serum cytokine changes in systemic vasculitis.

Cytokines are known to alter a number of vascular tissue cell functions. The aim of this retrospective study was to determine serum cytokine levels in patients with vasculitis and to analyse the possible relation to the severity of the disease. Tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1)beta, IL-2, interferon (IFN)- and IFN-gamma were assayed in 33 patients with polyarteritis nodosa (PAN) or Churg and Strauss angiitis (CSA), and three with Wegener granulomatosis (WG). Serum cytokine changes were observed in most patients with active disease, i.e. before treatment was started. In the majority of patients with PAN or CSA, there was a marked increase in serum IFN-alpha and IL-2 levels, while TNF-alpha and IL-beta levels were moderately elevated. Serum IFN-gamma remained undetectable in all but one of these patients. In patients with WG, serum IFN-alpha and IL-2 levels were also elevated, whereas IL-1 beta, IFN-gamma and TNF alpha levels remained within normal limits. In paired samples of patients with PAN, IFN-alpha and IL-2 levels were significantly higher before than after treatment. These preliminary data suggest that a particular pattern of cytokine changes is associated with vasculitis and that cytokines might be involved in the pathogenesis of PAN/CSA and WG. Prospective studies are warranted to determine whether cytokines could be considered for the monitoring of disease activity and therapy.     

Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): specific up-regulation by tumour necrosis factor-alpha (TNF-alpha) in synovial fluid.

This study was designed to investigate VEGF production from peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) compared with healthy controls and to identify the predominant cellular source in PBMC isolated from RA patients. The regulation of PBMC VEGF production by cytokines and synovial fluid (SF) was studied. PBMC were isolated from RA patients and healthy controls and stimulated with lipopolysaccharide (LPS), IL-1beta, IL-4, IL-6, IL-8, IL-10, TNF-alpha and transforming growth factor-beta (TGF-beta) isoforms for varying time points up to 72 h at 37 degrees C/5% CO2. The effect of SF on VEGF secretion by PBMC was also studied. Supernatant VEGF levels were measured using a flt-1 receptor capture ELISA. RA patients had significantly higher spontaneous production of VEGF compared with controls, and monocytes were identified as the predominant cellular source. RA PBMC VEGF production was up-regulated by TGF-beta isoforms and TNF-alpha and down-regulated by IL-4 and IL-10, with no effect observed with IL-1beta, IL-6 and IL-8. Antibody blocking experiments confirmed that TNF-alpha and not TGF-beta isoforms in SF increased VEGF secretion by RA PBMC. These results emphasize the importance of monocytes as a source of VEGF in the pathophysiology of RA. Several cytokines known to be present in SF can modulate the level of VEGF secretion, but the predominant effect of SF in VEGF up-regulation is shown to be dependent on TNF-alpha.     

Modulating Effects of Intravenous Immunoglobulins on Serum Cytokine Levels in Patients with Primary Hypogammaglobulinemia

BACKGROUND: Intravenous immunoglobulins (IVIG) have usually been administered for replacement therapy of humoral immunodeficiencies, but their use in treating other disorders with an immune pathogenesis is increasing. The exact mechanism of action by which IVIG are of benefit in such diseases is complex and only partly understood. One of the proposed mechanisms of action is the modulation of cytokine release. METHODS: We selected 29 patients with primary hypogammaglobulinemia (common variable immunodeficiency), receiving long-term substitutive therapy with IVIG, and 14 healthy blood donors as a control group. Blood samples were then taken before and 1 hour after finishing the IVIG infusion. Only one blood sample was obtained from the healthy controls. The cytokines studied were interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. RESULTS: Patients with primary hypogammaglobulinemia showed significantly higher serum levels of IL-6, IL-8, IL-1Ra, and TNF alpha than healthy controls. IVIG infusion significantly increased serum concentration levels of IL-6, IL-8, IL-1Ra, and TNF alpha. No significant variation was observed in serum levels of IL-beta, IFN gamma, or IL-2 after IVIG infusion. Age, IVIG commercial preparation, and IVIG dose did not influence cytokine serum levels. Moreover, a significant correlation was observed between serum level variations of IL-1Ra and TNF alpha, as well as an associative trend between maximum changes in IL-6 and IL-8 concentrations. CONCLUSIONS: IVIG administration significantly alters the serum pattern of selected cytokines, which might explain, at least in part, the mechanism of action of IVIG in autoimmune or inflammatory disorders.     

TH2 Cytokine-enhanced and TGF-beta-enhanced vascular endothelial growth factor production by cultured human airway smooth muscle cells is attenuated by IFN-gamma and corticosteroids

BACKGROUND: T(H)2 and T(H)1 cytokines have opposite effects on many aspects of the inflammatory response. METHODS: This study was designed to determine if cytokines possibly present in asthma can modulate airway smooth muscle cell (ASMC) production of vascular endothelial growth factor (VEGF) and thus contribute to altered airway vascularity. ASMC were incubated for 24 hours with various concentrations of T(H)2 cytokines (IL-4, IL-5, IL-10, and IL-13); transforming growth factor (TGF)-beta1, TGF-beta2, or TGF-beta3; and IL-1beta or TNF-alpha with or without IFN-gamma. Budesonide and exogenous prostaglandin (PG)E(2) were also evaluated. Postculture media were assayed for VEGF and PGE(2) by ELISA. RESULTS: IL-4, IL-5, and IL-13 alone but not IL-10 enhanced VEGF production by ASMC in a concentration-dependent manner. IFN-gamma alone inhibited spontaneous VEGF release by ASMC and concentration-dependently attenuated IL-4-augmented, IL-5-augmented, or IL-13-augmented production of VEGF (P <.01). All three TGF-beta isoforms augmented VEGF production, which was reduced by IFN-gamma (P <.005). IL-1beta also increased VEGF production, but this was not affected by IFN-gamma (P >.05). TNF-alpha alone had little effect on VEGF release by ASMC. Production of VEGF stimulated by all cytokines was inhibited by budesonide. Exogenous PGE(2) increased VEGF release, but cytokine modulation of PGE(2) release did not always correlate with VEGF release. CONCLUSIONS: T(H)2 cytokines and TGF-beta stimulate ASMC release of VEGF. This can be inhibited by IFN-gamma and glucocorticoids.