氯沙坦对心力衰竭病人肿瘤坏死因子的影响

目的 :研究氯沙坦对心力衰竭 (CHF)病人血肿瘤坏死因子 (TNF α)、内皮素 (ET 1)、醛固酮(Ald)水平的影响。方法 :采用放免法测定CHF病人 (5 4例 )及健康志愿者 (2 8例 )血TNF α ,Ald及ET 1水平。 5 4例CHF病人分为 2组 ,非氯沙坦组给予常规抗心力衰竭治疗 ;氯沙坦组在非氯沙坦组药物治疗基础上加氯沙坦 2 5～ 5 0mg·d- 1,共 1mo。结果 :CHF病人TNF α ,Ald及ET 1水平分别为(2 .7±s 0 .8) μg·L- 1,(195± 33)ng·L- 1,(90±16)ng·L- 1,显著高于健康对照组 [(1.2± 0 .2 ) μg·L- 1,(117± 38)ng·L- 1,(5 9± 11)ng·L- 1,P <0 .0 1];氯沙坦组经治疗后TNF ,Ald及ET 1水平显著降低 ;非氯沙坦组治疗后血Ald水平明显降低(P <0 .0 1)。结论 :氯沙坦可明显降低心力衰竭病人血TNF α及ET 1水平     

慢性心力衰竭患者血清sVCAM-1及TNF-α的测定与临床意义

目的:探讨慢性心力衰竭(CHF)患者血清可溶性血管细胞粘附分子-1(sVCAM-1)、肿瘤坏死因子α(TNF-α)浓度的变化并探讨其临床意义.方法:选取CHF患者61例,正常对照组25例.采用ELISA法测定其血清sVCAM-1浓度,采用放射免疫分析法测定其血清TNF-α浓度.结果:与正常对照组相比,CHF组血清sVCAM-1、TNF-α水平显著升高(P<0.01),sVCAM-1、TNF-α水平随心功能不全的加重而明显升高.各病因组之间sVCAM-1、TNF-α水平比较无显著性差异(P>0.05).血清sVCAM-1与血清TNF-α呈正相关(r=0.282, P<0.01).结论:CHF患者血清sVCAM-1、TNF-α水平明显升高,并与CHF严重程度有关,提示sVCAM-1、TNF-α可能在CHF的发病机制中起了重要作用.     

氨氯地平在心衰治疗中对肿瘤坏死因子-α、白细胞介素-1,6的作用

目的 :探讨氨氯地平在心力衰竭 (心衰 )治疗中对细胞因子的作用。方法 :选择扩张型心肌病和缺血性心脏病心衰病人共 6 0例 ,随机分成常规组与氨氯地平组。常规组给予常规抗心衰治疗 ,氨氯地平组在常规治疗基础上加用氨氯地平 5mg ,po ,qd。同时建立正常组。检测肿瘤坏死因子 α(TNF α)、白细胞介素 1(IL 1)、白细胞介素 6 (IL 6 )。结果 :IL 1,IL 6 ,TNF α在心衰病人中分别达 (30±s 13) ,(99± 4 3)和 (2 4± 5 )ng·L- 1,较正常人[(6 .1± 1.7) ,(2 9± 8) ,(16± 5 )ng·L- 1]明显增高(P <0 .0 1)。治疗 6wk后 ,氨氯地平组病人较常规组IL 6 ,TNF α明显降低 ,分别为 (45± 2 4 )和 (17±5 ) ,(6 0± 31)和 (2 0± 4 )ng·L- 1(P <0 .0 1)。结论 :氨氯地平治疗心衰的作用之一可能在于降低细胞因子如IL 6和TNF α的水平     

心力衰竭患者血浆中肿瘤坏死因子及一氧化氮水平的变化

目的 探讨肿瘤坏死因子-α（TNF-α）、可溶性肿瘤坏死因子受体（sTNFR）及血浆一氧化氮（NO）在充血性心力衰竭（CHF）发生和发展中的作用与相互关系。方法 用断面调查的方法,采用双抗体夹心法测定了68例CHF患者血浆中TNF-α和sTNFR水平,用高效液相法测定了血浆NO的变化,并与30例正常人进行对照。结果 检测结果表明,不同程度的 CHF患者血清中上述指标均发生明显的改变,与对照组比较存在显著差异（P<0.01）,TNF-α,sTNFR和NO三者之间存在明显正相关,并随心力衰竭程度的加重而增加。结论TNF-α及NO水平的变化是影响CHF发生和发展的重要因素。     

Design of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) for chronic inflammatory diseases

A recombinant C-terminal truncated form of the human soluble tumor necrosis factor receptor type I (sTNF-RI) was produced in E. coli. This soluble receptor contains the first 2.6 of the 4 domains of the intact sTNF-RI molecule. A monoPEGylated form of this molecule was produced using a 30 kD methoxyPEG aldehyde with approximately 85% selectivity for the N-terminal amino group. This molecule was shown to be less immunogenic in primates than the full length (4.0 domain) molecule or other versions of sTNF-RI which were either PEGylated at different sites or with different molecular weight PEGs. The 30 kD PEG also has a longer serum half-life to the molecule than lower molecular weight PEGs. This molecule markedly blunts the inflammatory response in a number of rheumatoid arthritis animal models. In addition, phase I/II and early phase II data in humans indicate that PEG sTNF-RI is non-immunogenic and that weekly dosing with this drug can reduce the number of tender and swollen joints in rheumatoid arthritis patients. PEG sTNF-RI has comparable American College of Rheumatology (ACR) efficacy scores as other anti-TNF molecules currently used to treat rheumatoid arthritic patients.     

Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer

Most cases of cervical cancer are the result of infection with specific high-risk types of human papillomavirus (HPV). Investigating the genetic basis of the host immune response, particularly cytokine function, could help further characterize the progression of cervical HPV infection into neoplasia. Prior studies have demonstrated a correlation between genetic variants of tumor necrosis factor alpha (TNF-α, TNF gene) and/or interleukin-10 (IL-10, IL10 gene) and cervical cancer susceptibility. However, some of the results have been contradictory. We sought to resolve these discrepancies by carrying out our study in a large cohort of Chinese women. In order to assess the association of TNF and IL10 genotypes with cervical cancer susceptibility, the polymorphisms in TNF (-238 G/A, -308 G/A) and IL10 (-592 C/A, -819 C/T, -1082 A/G) were genotyped and odds ratios for the genotype and allele frequencies between cervical cancer patients and healthy controls were calculated. Also, the functional relevance of these polymorphisms was evaluated using enzyme-linked immunosorbent assays (ELISAs) and in vitro lymphocyte proliferation assays. The TNF-238 AA genotype frequency was lower in patients than in controls (p < 0.05). TNF-308 AA, IL10-592 CA/AA, and IL10-819 CC/CT genotype frequencies were higher in cervical cancer patients than in controls (p < 0.05). The frequency of the TNF-238 A allele was significantly lower in patients, while the frequency of the -308 A allele was significantly higher (p < 0.05). No significant differences between patients and controls were found in the genotype or allele frequencies of IL10-1082 A/G (p > 0.05). Furthermore, the combinations of TNF-238 GA or GG and IL10-592 CC; TNF-238 GA or GG and IL10-592 CA or AA; TNF-308 AA and IL10-592 CC; and TNF-308 AA and IL10-592 CA or AA in cervical cancer patients were statistically significant (p < 0.0167). Upon stimulation with PHA, peripheral blood mononuclear cells (PBMCs) with the TNF-308AA genotype exhibited significantly higher proliferation rates, elevated IL-4, TGF-β levels, and lower IL-2 levels (p < 0.05). For IL10-592C/A, the AA and CA genotypes were significantly associated with higher proliferation rates, elevated IL-4 and IL-10 levels (p < 0.05). We also found that for TNF-308 G/A or IL10-592 C/A variants, the combination of TNF-308 GG or GA with IL10 CA or AA had an association with the severity of cervical cancer. Taken together, these results suggest that TNF-308 AA and IL10-592 CA/AA genotypes may increase susceptibility to cervical cancer by altering the immune response of an individual.     

Corticotropin-releasing factor (CRF) and interleukin-1 (IL-1) receptors in the brain-pituitary-immune axis

Corticotropin-releasing factor (CRF) and interleukin-1 (IL-1) are two major components of the brain-endocrine-immune response to stress. We identified, characterized, and localized CRF and IL-1 receptors in brain, pituitary, and spleen using 125I-CRF and 125I-IL-1 alpha, respectively. 125I-CRF binding had comparable kinetic (KD:200-400 pM) and pharmacological characteristics in brain, pituitary, and spleen. In studies using cross-linking techniques, 125I-CRF was incorporated in rat pituitary and mouse spleen homogenates into a complex of Mr = 75,000 and in rat brain, into a complex of Mr = 58,000. The differences observed in the molecular weights between the pituitary and splenic vs. brain CRF receptors were evident across a variety of species and appeared to be due to differential glycosylation of the receptor proteins. In autoradiographic studies, CRF receptors were localized in highest densities in anterior pituitary and in brain regions involved in cognitive function, in limbic areas involved in emotion, and in brain areas regulating autonomic and other stress-related responses. In spleen, CRF binding sites were localized in the macrophage-rich red pulp and marginal zone surrounding the white pulp regions. High affinity 125I-IL-1 alpha binding sites were identified in pituitary membranes with kinetic and pharmacological characteristics comparable to the well-characterized IL-1 receptors in the EL-4 6.1 mouse thymoma cell line. Preliminary studies have identified IL-1 receptors in discrete regions of mouse brain. These data further substantiate the physiological role of CRF and IL-1 in modulating the brain-endocrine-immune axis.     

肺心病心力衰竭患者血清肿瘤坏死因子和一氧化氮的含量变化

目的探讨TNF-α、NO在肺心病心力衰竭病理生理过程中的作用。方法用放射免疫法测定血清TNF-α含量,用硝酸还原酶法测定血清NO含量,用彩色多普勒诊断分析仪测定左、右心室射血分数（LVEF、RVEF）、肺动脉收缩压（PASP）。结果肺心病心衰患者血清TNF-α、NO含量明显高于对照组（P＜0．01）。肺心病不同心功能组TNF-α、NO明显不同,各组间比较有差异有统计学意义（P＜0．01）．升高幅度与心力衰竭程度呈正相关。TNF-α、NO与PASP呈显著正相关（P＜0．01）,与RVEF、LVEF呈显著负相关（P＜0．01）。结论肺心病心衰患者TNF-α、NO含量明显升高,TNF-α对心肌起负性肌力作用,在心脏收缩功能障碍中起重要的作用。     

慢性乙型肝炎患者拉米夫定治疗前后SIL-2R、TNF和T淋巴细胞亚群的变化

目的　研究拉米夫定对慢性乙型肝炎患者SIL 2R(可溶性白细胞介素 2受体 )、TNF(肿瘤坏死因子 )和T淋巴细胞亚群的影响。方法　分别用双抗体夹心酶联免疫法测血清SIL 2R、放射免疫法测血清TNF和单克隆抗体免疫技术测定T淋巴细胞亚群 ,比较拉米夫定治疗 35例慢性乙型肝炎患者治疗前后HBVDNA阴转率、ALT复常率、SIL 2R、TNF和T淋巴细胞亚群的变化。结果　治疗后HBVDNA阴转率为 86 .9% ,ALT复常率为 79.8% ,显著高于治疗前 (P <0 .0 1)。SIL 2R、TNF水平显著降低 (P <0 .0 5 )。T淋巴细胞亚群CD 4 、CD 4 /CD 8水平显著高于治疗前 (P <0 .0 1) ,CD 8显著低于治疗前 (P <0 .0 5 )。HBVDNA阴转者T细胞免疫功能优于未转者。结论　拉米夫定可改善慢性乙型肝炎的细胞因子水平和T细胞免疫功能 ,T细胞免疫功能紊乱较轻的患者 ,拉米夫定治疗的效果较好 ,SIL 2R、TNF及CD 4 /CD 8水平可以作为疗效判断的指标。这些指标在一定程度上反映了机体免疫功能状态和肝脏受损的程度 ,具有较高的临床价值     

Development of high-throughput radioligand binding assays for interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor (TNF-alpha) in isolated membrane preparations.

Cytokine binding has been studied in a variety of intact cells, and in isolated receptor preparations. Each approach is associated with limitations with regard to screening large numbers of samples on a repetitive basis. In order to provide a more reproducible system of screening for compounds which modify IL-1 alpha and TNF-alpha binding, we have developed isolated membrane preparations for studying agents which can alter the association of these ligands with their receptors. These results demonstrate IL-1 alpha binding to BALB/c 3T3 cell membranes and TNF-alpha binding to HeLa S3 cell membranes, and indicate that this is a viable approach to high-throughput screening.     

Xiang-qi-tang increases avian pathogenic Escherichia coli-induced survival rate and regulates serum levels of tumor necrosis factor alpha, interleukin-1 and soluble endothelial protein C receptor in chicken

Xiang-qi-tang (XQT) is a Chinese herbal formula containing rhizoma Cyperi, Andrographis paniculata and Astragalus membranaceus. The present study investigated the effects of XQT on the mortality and inflammatory mediators in a chicken model challenged with avian pathogenic Escherichia coli (APEC). To detect the effect of XQT, the chickens were pretreated with the formula 12 h before being challenged with 10(8) colony forming unit (CFU) of APEC. The results showed that 0.6 g/kg XQT significantly elevated the survival rate of infected chickens. To further investigate the mechanism of decreasing mortality of XQT, we examined plasma inflammatory mediator levels. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1) and soluble endothelial protein C receptor (sEPCR) were significantly increased in chickens challenged with APEC alone, whereas chickens pretreated with 0.6 g/kg XQT showed marked decrease of these inflammatory mediator levels during the death peak. Taken together, this study demonstrates that XQT has protective effects in APEC-treated chickens. The action mechanisms of XQT involve anti-inflammation and antithrombotic activity. These findings may contribute to future research on the action mechanisms of this formula, as well as prevention of or therapy for avian colibacillosis.     

Water immersion (WI) induced alterations of plasma vasopressin (AVP) levels in patients with noninflammatory acute renal failure (NARF) and in patients with chronic renal failure (CRF)

Water immersion (WI) induced alterations of plasma vasopressin (AVP), plasma osmolality, plasma volume (PV) and plasma sodium and potassium concentration were examined in 12 patients with noninflammatory acute renal failure (NARF) at the anuric/oliguric phase, 20 patients with chronic renal failure (CRF) and 15 healthy persons. In all examined groups a significant increase of PV and decrease of plasma osmolality and AVP after WI was observed. In patients with NARF the increase of PV was significantly greater than in CRF and in healthy persons. In patients with NARF a significantly greater decrease of plasma sodium concentration after WI was also noted than in patients with CRF and in healthy persons. Only in healthy persons, but not in patients with acute or chronic renal failure a significant correlation between PV or decrease of plasma osmolality and WI induced decrease of plasma AVP level was stated. We conclude that patients with NARF and CRF are characterized by an inappropriate volumetric and osmotic regulation of AVP secretion.     

不同麻醉方式对全髋置换术患者炎性细胞因子的影响

目的　双盲对比观察硬膜外麻醉与全麻下全髋置换手术病人围术期血清肿瘤坏死因子( TNF- α)、白细胞介素 - 6 ( IL- 6 )、白细胞介素 - 8( IL- 8)、白细胞介素 - 10 ( IL- 10 )水平的动态变化 ,分析手术麻醉对患者免疫力的影响。方法　选择 30例 ASA ～ 级择期行全髋置换术的病人 ,按麻醉方式的不同随机分成硬膜外麻醉组及全麻组 (每组 15例 ) ,记录术中患者生命体征、手术时间、术中的出血量与输血量及不同时间 ,外周血清中 TNF-α、IL - 6、IL - 8、IL - 10水平。结果　所有患者术中血流动力学指标均稳定。两组 TNF-α没有明显变化 ;硬膜外麻醉组 IL - 6在手术开始后 30 min及术毕明显升高 ( P<0 .0 5 ) ;IL - 8在术后第 1天达高峰 ,至术后第 2天仍高于正常 ;IL- 10在术后第 1天、第 2天水平较术前明显下降 ( P<0 .0 5 ) ;全麻组 IL- 6在手术开始后 30 min及术毕升高 ,与术前值比较差异无显著性 ( P>0 .0 5 ) ,但明显小于硬膜外麻醉组同时点值 ( P<0 .0 5 ) ,IL- 8在术后第 1天达高峰 ,至术后第 2天恢复于术前水平 ;IL- 10在术后第 1天、第 2天水平较术前有所下降 ,但差异无显著性。结论　手术创伤可引起促炎性细胞因子释放增加及抗炎性细胞因子分泌的不足 ,全身麻醉能更好地抑制促炎性细胞因子的释?     

Circulating levels of advanced glycation end products (AGE) and interleukin-6 (IL-6) are independent determinants of serum asymmetric dimethylarginine (ADMA) levels in patients with septic shock

There is a growing body of evidence that nitric oxide (NO) excess plays a central role in the pathogenesis of hypotension and organ failure in patients with septic shock. In addition, recently, asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been shown to contribute to the regulation of vascular tone via modulation of NO generation in vivo. However, the kinetics and regulation of serum levels of ADMA in patients with septic shock are largely unknown. Since high mobility group box 1 (HMGB1)-receptor for advanced end products (RAGE) axis is supposed to be involved in the lethality in septic shock, we examined the correlations among serum levels of ADMA, endotoxin, interleukin-6 (IL-6), soluble form of RAGE (sRAGE) and RAGE ligands such as HMGB1 and advanced glycation end products (AGE) in septic shock patients. Fifteen septic shock patients (10 males and 15 females, mean age: 70.1 ± 8.5 years) and fifteen age- and sex-matched healthy volunteers were included in this study. The criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were used for diagnosis of septic shock. All the subjects underwent a complete history and physical examination, determination of blood chemistries, including serum levels of ADMA, endotoxin, IL-6, HMGB1, AGE and sRAGE. Linear and multiple stepwise regression analysis were performed for the determinants of serum levels of ADMA. Serum levels of ADMA were significantly higher than those in healthy volunteers (0.98 ± 0.21 nmol/mL vs. 0.30 ± 0.05 nmol/mL, p < 0.0001). In univariate analysis, creatinine (p < 0.005), endotoxin (p < 0.001), IL-6 (p < 0.001), HMGB1 (p < 0.001), AGE (p < 0.001) and sRAGE (p < 0.001) were significantly associated with serum ADMA levels. After performing multivariate stepwise regression analyses, IL-6 (p = 0.001), AGE (p = 0.002) and creatinine (p = 0.013) still remained significant independently. The present study is the first demonstration that ADMA levels were significantly elevated in patients with septic shock and that serum IL-6, AGE and creatinine levels were independent determinants of ADMA in these patients. Given the harmful effects of NO excess in septic shock, ADMA levels may be increased as a counter-system against inflammation and oxidative stress in this life-threatening disorder.     

曲美他嗪对慢性心力衰竭患者血清CA125、IL-6及BNP的作用

目的 观察曲美他嗪对慢性心力衰竭(CHF)患者血清CA125、IL-6及BNP的影响,探讨曲美他嗪治疗CHF的临床疗效.方法 选取本院2012年9月至2015年9月收治的CHF患者160例,随机分为对照组及观察组,各80例.对照组予以标准的CHF药物治疗,观察组在标准CHF药物治疗基础上联合曲美他嗪治疗,疗程3个月.观察治疗前后症状的改善情况,根据纽约心功能(NYHA)分级进行疗效评价,并检测血清糖类抗原125(CA125)、白介素-6(IL-6)及B型钠尿肽(BNP)的表达变化.结果 治疗前两组患者年龄、性别及心功能分级,差异无统计学意义(t=-0.272,P=0.786;x2=0.223,P=0.633;x 2=0.503,P=0.778).观察组临床疗效总有效率90.0％,明显优于对照组的81.3％(x 2=7.047,P=0.030).两组治疗后血清CA125、IL-6及BNP的表达均下调(P＜0.001),观察组血清CA125、IL-6及BNP表达较对照组明显下降(t=5.270、8.960、10.523,P＜0.001).结论 曲美他嗪治疗CHF疗效显著,可显著改善患者NYHA分级,并能降低血清CA125、IL-6及BNP的表达.     

IL-10及TNF—α在慢性阻塞性肺疾病急性加重期患者血清及痰液中升高的意义

目的观察白介素-10（IL-10）及肿瘤坏死因了-α（TNF—α）在慢性阻塞性肺疾病急性加重期（AECOPD）患者血清及痰液的表达,从而探讨AECOPD与免疫机制中细胞因子的关系。方法收集26名AECOPD患者作为观察组,22名健康体检者作为对照,用ELISA法分别检测其血清及痰液IL-10及TNF—α的含量。结果观察组患者血清及痰液的IL-10含量均较对照组升高,但两组患者的血清IL-10含量差异无统计学意义（P=0．071）,而观察组的痰液IL-10显著高于对照组（P=0．034）;观察组的TNF-α含量均比对照组升高,两组患者血清和痰液TNF—α水平差异具有统计学意义（P=0．023,P=0．008）。结论IL-10与TNF—α升高可能与AECOPD的免疫机制有关。     

原发性高血压患者血清IL-6和C-反应蛋白水平的研究

目的：探讨在原发性高血压患者中,血清C-反应蛋白（CRP）和白细胞介素-6（IL-6）水平变化及意义。方法：选择42例正常血压人群和36例原发性高血压患者,常规测量血压,抽取空腹静脉血检测其血糖、血脂、胰岛素、IL-6、CRP。结果：与正常人群相比,在高血压患者中,血清总胆固醇、三酰甘油、空腹胰岛素、IL-6水平（14.56±5.36vs23.16±2.43μg/ml,P〈0.05）、CRP（1.52±1.04vs2.05±1.47mg/ml,P〈0.05）水平均高于正常血压人群。在原发性高血压患者中,血清IL-6、CRP水平均与体重指数、收缩压正相关。结论：原发性高血压患者中血清IL-6、CRP水平增高并与收缩压正相关,提示原发性高血压与炎症密切相关。     

四逆汤对失血性家兔肿瘤坏死因子的影响

目的:探讨中药四逆汤对失血性休克家兔肿瘤坏死因子的影响。方法:采用动物分组对照实验,测量不同状态下动物血浆肿瘤坏死因子的变化。结果:与休克前比较,休克组的家兔血浆肿瘤坏死因子水平各时段均明显提高(P<0.01),而治疗组仅在治疗后30min家兔肿瘤坏死因子水平均明显提高(P<0.05),而其他时段与休克前比较未见显著差异(P>0.05)其他时段与休克前比较,虽有升高但无显著性差异(P>0.05),两组间各时段比较,未见显著性差异(P>0.05)。     

慢性肾功能衰竭患者血清瘦素水平的变化及其意义

目的探讨慢性肾功能衰竭(chronicrenalfailure,CRF)患者血清瘦素(Leptin)水平,并观察瘦素与肾功能(BUN、SCr、UA、CCr)、人体营养指标(TP、ALB、Chol、HCT、RBC、Hb、PCR、BMI)之间的关系。方法以放射免疫分析法测定68例CRF患者血清瘦素的浓度,并与健康组进行比较,分析瘦素与肾功能之间的关系。同时测定患者的血浆蛋白、血常规及身高与体重,计算CCr、PCR。结果健康组血清瘦素浓度为(1.9543±0.4721)μg/L,CRF患者血清瘦素浓度为(2.8668±0.9026)μg/L,与健康组比较具有极显著差异(P<0.01);在CRF患者不同分期中,血清瘦素浓度随CCr的下降而升高,Leptin与SCr、UA水平呈正相关(P<0.05或P<0.01),与CCr、TP、RBC、Hb、PCR水平呈负相关(P<0.05或P<0.01),与年龄、BUN、ALB、Chol、HCT、BMI之间未发现有显著性差异。结论慢性肾功能衰竭时血清瘦素水平明显升高,其升高程度与肾功能的恶化具显著相关性。高瘦素血症可导致患者营养不良,血清瘦素可作为评价人体营养状况的一个重要指标。