卡托普利注射液对充血性心力衰竭细胞因子的干预作用

目的　探讨血管紧张素转换酶抑制剂 (ACEI)对心力衰竭 (CHF)患者血清肿瘤坏死因子 -α(TNF-α) ,白细胞介素 - 6 (IL- 6 ) ,白细胞介素 - 10 (IL- 10 ) ,一氧化氮 (NO)的干预影响。方法　将 5 5例 CHF患者分为治疗组和常规组。常规组采用常规治疗 ,治疗组在常规治疗基础上用卡托普利注射液治疗 1周 ,在治疗前与治疗后测定 TNF-α,IL- 6 ,IL- 10 ,NO的变化。结果　治疗后两组血清 TNF- α,IL- 6 ,NO水平均明显下降 (P<0 .0 5 ,P<0 .0 1,P<0 .0 1) ;治疗前血清 IL - 10水平较对照组升高无显著性差异 (P>0 .0 5 ) ,治疗后 IL - 10水平明显升高 (P<0 .0 5 ) ;治疗组治疗后上述指标降低或升高的幅度显著高于常规组治疗后降低或升高的幅度 (P<0 .0 5 )。结论　 ACEI可能通过调控细胞因子的浓度来改善心功能 ,为其治疗心力衰竭进一步提供理论依据     

心力衰竭患者炎性与抗炎性细胞因子表达的平衡失调

目的 :了解炎性与抗炎性细胞因子在充血性心力衰竭 (CHF)过程中的变化及其临床意义。方法 :用双抗体夹心ELISA法测定 12 2例CHF患者及 30例健康人血浆中肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )的浓度。结果 :①CHF患者血浆中TNF α水平明显高于对照者 (P <0 .0 5或 <0 .0 1) ,且随着心力衰竭程度的加重 ,TNF α水平呈进行性增高 ;CHF患者血浆IL 6及IL 10水平 ,心功能Ⅲ、Ⅳ级者明显高于对照者 (P <0 .0 5或 <0 .0 1) ,而心功能Ⅱ级者与对照者相比差异无显著性意义。②TNF α与IL 6 (r =0 .6 18,P <0 .0 1)、IL 10 (r =0 .5 6 6 ,P <0 .0 1)均呈正相关 ,但TNF α与IL 10的比率 (TNF α/IL 10 )也随着心功能的恶化而升高 ,IL 10的升高与TNF α的升高相比明显不足。结论 :细胞因子的变化与心力衰竭的严重程度密切相关 ,CHF患者血中炎性细胞因子明显升高的同时伴有抗炎性细胞因子升高的相对不足 ,炎性与抗炎性细胞因子之间的平衡失调可能参与了CHF的发生发展     

辨证论治充血性心力衰竭与细胞因子的相关性研究

综述中医辨证施治充血性心力衰竭与细胞因子肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1)、白细胞介素6(IL-6)的相关性.     

肿瘤坏死因子-α、白细胞介素-1 β、-6水平与充血性心力衰竭关系的临床研究

目的探讨肿瘤坏死因子α(TNFα)、白细胞介素1β(IL1β)、白细胞介素6(IL6)与充血性心力衰竭(CHF)的关系。方法采用放射免疫分析法(RIA)测定三组入选者血清TNFα、IL1β、IL6的含量,CHF心功能Ⅰ、Ⅱ级组(30例),CHF心功能Ⅲ、Ⅳ级组(30例),对照组(28例)。结果心功能Ⅲ、Ⅳ级组患者血清TNFα、IL1β、IL6含量显著高于对照组(P<0.01)和心功能Ⅰ、Ⅱ级组(P<0.05),心功能Ⅰ、Ⅱ级组显著高于对照组(P<0.01);TNFα与IL1β、IL6呈显著正相关(r1=0.763,r2=0.684均P<0.01)。结论TNFα、IL1β、IL6水平与CHF发生发展密切有关。     

细胞因子与充血性心力衰竭

细胞因子参与并介导了充血性心力衰竭的发生和发展，针对细胞因子的抗免疫治疗可成为治疗心力衰竭的新途径。     

培哚普利对老年充血性心力衰竭患者血清炎性细胞因子的影响

目的 观察培哚普利对老年充血性心力衰竭(CHF)患者血清中肿瘤坏死因子(TNF—α)、白细胞介素—1(IL-1β)、白细胞介素-6(IL-6)的影响．方法 放免法检测53例老年CHF患者(培哚普利组28例，常规治疗组25例)治疗前后及25例健康老年人血清中TNF-α、IL-1β、IL—6水平．结果 老年CHF患者血清中TNF—α、IL-1β、IL—6水平显著高于对照组(P＜0．01)，且随着心功能损害程度加重而升高，TNF—α、IL—6水平在心功能各组间比较有显著性差异(P＜0．05)，IL—1β水平在心功Ⅳ级显著高于心功能Ⅱ、Ⅲ级(P＜0．05)．培哚普利组与常规治疗组老年CHF治疗后血清炎性细胞因子浓度均有明显降低，但培哚普利组TNF—α、IL-1β、IL—6水平下降更为明显(P＜0．05)。结论 血清中TNF—α、IL—1β、IL-6水平可反映心力衰竭的程度；培哚普利可明显降低老年CHF患者血清TNF—α、IL-1β、IL—6水平，从而保护和改善心脏功能．     

细胞因子在充血性心力衰竭诊疗中的应用

充血性心力衰竭(congestive heart failure，CHF)实质上是由于能量不足造成基因表达异常而引起的一种超负荷性心肌病．其患病率高，死亡率大．5年存活率与恶性肿瘤相仿。近年来研究发现，细胞因子在CHF的发病过程中起着重要作用。本就细胞因子在CHF诊疗中的应用概述如下。     

多器官功能障碍综合征血清炎性细胞因子变化的意义

目的 :探讨多器官功能障碍综合征 (MODS)血清炎性细胞因子的变化的意义。方法 :采用双抗体夹心酶联免疫吸附法测定 42例MODS和 3 0例健康对照组的血清肿瘤坏死因子 (TNF α)、白介素 1β(IL 1β)与白介素 6(IL 6)含量。结果 :MODS血清TNF α、IL 1β与IL 6含量 (各为2 77.64±5 4.3 6ng/L ,2 40 .97± 2 0 .87ng/L ,3 84.96± 73 .19ng/L)明显高于对照组 ( 2 3 .3 7± 7.96ng/L ,40 .65± 5 .87ng/L ,3 0 .2 6± 3 .61ng/L) ,P均 <0 .0 0 1;死亡组TNF α、IL 1β与IL 6含量 (各为5 5 4.86± 95 .69ng/L ,3 3 8.87± 41.2 1ng/L ,5 97.3 7± 118.3 6ng/L)高于非死亡组TNF α、IL 1β与IL 6含量 ( 2 77.64± 5 4.3 6ng/L ,2 40 .97± 2 0 .87ng/L ,3 84.96± 73 .19ng/L) ,P均 <0 .0 1。结论 :TNF α、IL 1β与IL 6对MODS的病理生理过程可能起作用 ,监测MODS患者血清TNF α、IL 1β与IL 6水平可作为反映病情严重程度和评估预后的一项参考指标     

心功能不全病人血浆细胞因子的变化及其临床意义

目的:探讨不同病因的慢性心功能不全(CHF)病人及CHF的不同阶段,促炎细胞因子的变化及临床意义。方法:以双抗夹心EL ISA法测定71例CHF病人及50例健康人血浆中肿瘤坏死因于-α(TNF-α)和白细胞介素-6(IL-6)的浓度。结果:CHF病人血浆TNF-α和IL-6水平明显高于对照组(P<0.01),且与心功能Ⅱ级病人相比较,心功能Ⅳ级病人的TNF-α和IL-6明显增高(P<0.01),而三种心脏病之间,FNF-α和IL-6的测定无明显的差异。结论:CHF病人的血浆TNF-α和IL-6水平升高是心功能不全的免疫学标志之一,与病因无关,提示炎症机制参与了心力衰竭的进程。     

肿瘤坏死因子,白细胞介素—1在充血性心力衰竭发生发展中的作用

采用双抗体夹心ＥＬＩＳＡ法对５５例充血性心力衰竭（ＣＨＦ）患者和３０例正常对照者测定其血清肿瘤坏死因子α（ＴＮＦα）,白细胞介素１β（ＩＬ－１β）。结果：心功能Ⅲ级及Ⅳ级患者的ＴＮＦαＩＬ－１β较正常对照组和心功能Ⅱ级患者明显升高（Ｐ〈０．０１）。     

Proinflammatory cytokines in heart failure: double-edged swords

Increased circulating and intracardiac levels of proinflammatory cytokines have been associated with chronic heart failure. Following an initial insult, the increased production of proinflammatory cytokines, including TNF-α, IL-6, IL-1, and IL-18, jeopardizes the surrounding tissue through propagation of the inflammatory response and direct effects on the cardiac myocyte structure and function. Cardiac myocyte hypertrophy, contractile dysfunction, cardiac myocyte apoptosis, and extracellular matrix remodeling contribute enormously to the development and progression of chronic heart failure. Despite the identification of efficacious pharmacological regimens and introduction of mechanical interventions, chronic heart failure remains among the leading causes of mortality worldwide. To introduce novel therapeutic strategies that modulate the inflammatory response in the context of the failing heart, it is of prime importance to determine the contributions of TNF-α, IL-6, IL-1, and IL-18 in mediating cardiac adaptive and maladaptive responses, as well as delineating their downstream intracellular signaling pathways and their potential therapeutic implications.     

卡维地络对充血性心力衰竭患者促炎细胞因子的影响

目的：观察卡维地络对充血性心力衰竭（CHF）患者促炎细胞因子浓度的影响。方法：选择66例CHF患者，随机分为常规治疗组和卡维地络治疗组，32例健康体检者为正常对照组。用双抗体夹心ELISA法测定血浆肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）和IL-1β的浓度，分析其与CHF程度的关系。结果：（1）CHF患者三种细胞因子浓度均明显高于正常对照组（P〈0．05或〈0．01），CHF程度越重细胞因子浓度越高（P〈0．01）；（2）治疗后卡维地络组心功能分级左室收缩末内径较治疗前显著降低（P均〈0．05），左室短轴缩短率（LVFS）、每搏量（SV）、左室射血分数（LVEF）较治疗前显著升高（P〈0．05～〈0．01）；常规治疗组仅LVEF显著升高（P〈0．05）；治疗后卡维地络组LVEF、LVFS较常规治疗组显著升高（P〈0．05）；（3）治疗后卡维地络组三种细胞因子浓度显著降低（P〈0．01或〈0．05）；常规治疗组TNF—α、IL-6降低（P〈0．05），而IL-1β水平降低不显著。结论：CHF患者促炎细胞因子浓度升高，可作为判断心衰严重程度的指标。卡维地络能有效抑制促炎细胞因子的产生，改善心功能和心室重构。     

老年慢性心力衰竭患者细胞因子和心率变异性的相关性研究

目的 观察老年慢性心力衰竭(CHF)患者炎性细胞因子和心率变异性(HRV)的相关性.方法 128例60岁及以上老年CHF患者(CHF组),对照组50例为健康体检者.比较两组炎性细胞因子包括肿瘤坏死因子可溶性受体Ⅰ、Ⅱ(sTNF-RⅠ、sTNF-RⅡ)和白细胞介素6(IL-6)表达水平,24 h内的全部HRV参数[正常心动周期的标准差(SDNN)、24 h内5 min节段平均心动周期的标准差(SDANN)、24 h内全部5 min节段所有心动周期标准差的平均值(SDNNI)、相邻正常心动周期差值均方的平均根(rMSSD)和相邻两正常心动周期差值大于50 ms的个数所占的百分比(pNN50)],分析二者相关性.结果 CHF组患者HRV参数低于对照组:SDNN分别为(99.8±22.4)和(146.6±43.2)ms、SDANN分别为(85.5±23.6)和(138.7±40.9)ms、SDNNI分别为(41.7±15.8)和(56.9±18.8)ms、rMSSD分别为(23.4±13.0)和(30.0±12.9)ms、pNN50分别为(5.5±3.8)和(12.0±4.7)%;CHF患者炎性细胞因子明显高于对照组(均为P＜0.05);CHF患者HRV参数与炎性细胞因子浓度间呈负相关(r≥-0.44,P＜0.05).结论 炎性细胞因子sTNF-R Ⅰ、sTNF-RⅡ和IL-6可能是老年CHF患者HRV下降的原因之一.     

心力衰竭患者血浆细胞因子的变化及其临床意义

目的　探讨充血性心力衰竭 (心衰 ,CHF)患者血中肿瘤坏死因子 α(TNF α)和白细胞介素 6(IL 6)的变化及其临床意义。方法　双抗体夹心ELISA法测定 12 2例CHF患者及 3 0例健康人血浆中TNF α和IL 6的浓度。超声心动图测量左心室射血分数及左心室舒张末期内径 ,X线胸片测心胸比。结果　CHF患者血浆中TNF α水平明显高于对照组 (P <0 .0 5 ) ,且随着心衰程度的加重 ,TNF α水平呈进行性增高 ;IL 6水平仅在心功能Ⅲ级、Ⅳ级组中明显高于对照组 (P <0 .0 5 )。TNF α、IL 6与左心室射血分数呈负相关 (r =-0 .5 13 ,r =-0 .45 3 ,P <0 .0 1) ,与心胸比呈正相关 (r =0 .5 0 1,r =0 .43 8,P <0 .0 1) ;与左心室舒张末期内径呈正相关 (r =0 .3 42 ,r =0 .3 0 4,P<0 .0 1)。结论　CHF患者TNF α和IL 6升高可能是心功能恶化的免疫学标志之一 ,提示炎症机制参与心力衰竭的进程     

Proinflammatory cytokines, soluble Fas receptor, nitric oxide and angiotensin converting enzyme in congestive heart failure

We measured serum interleukin-2 receptor (sIL-2R), tumor necrosis factor-a (TNF-a), Fas receptor (sFas), nitric oxide (NO), and angiotensin converting enzyme (ACE) activity in 45 patients with congestive heart failure (CHF) of different etiologies. The relatioship between these bioindices and the severity of heart failure was analysed. Patients were classified according to the etiology of heart failure into: 15 patients with rheumatic valvular heart disease (RHD), 17 with ischemic heart disease (IHD) and 13 with idiopathic dilated cardiomyopathy (DCM). Patients were further classified according to severity of CHF following the New York Heart Association classification (NYHA) into: NYHA class II (n= 7), NYHA class III (n=20) and NYHA class IV (n=18). Eighteen healthy subjects were included as controls. Serum sIL-2R, TNF-alpha and sFas levels were determined by ELISA while serum NO and ACE levels were measured by colorimetric methods. Doppler Echocardiography was performed for all participants. Levels of sIL-2R, TNF-alpha, sFas, NO, and ACE were significantly higher in CHF patients than controls. Levels of the bioindices varied according to the CHF etiology. TNF-a level was the only one that had significant differences among different subgroups (RHD, IHD and DCM). The levels of sIL-2R, TNF-alpha, NO and sFas in patients with NYHA class IV were significantly higher than class II or III. Moreover, sIL-2R, TNF-alpha and NO levels were significantly higher in patients with diastolic dysfunction than patients with normal diastolic function. A significant positive correlations were found between sFas and both TNF-alpha and sIL-2R and between TNF-alpha and both NO and diastolic function. In addition, significant positive correlations were found between TNF-alpha and sIL-2R in both IHD and RHD patients and between sIL-2R and both ACE in IHD patients and diastolic function in DCM patients. It is concluded that a relationship exists between immune system activation, apoptosis and renin- angiotensin system in CHF and this may play a significant role in the pathophysiology and prognosis of the disease.     

Circulating interleukin-6 family cytokines and their receptors in patients with congestive heart failure

gp130 is a common signal-transducing receptor subunit for the interleukin (IL)-6 cytokine family. Studies in genetically engineered animal models have demonstrated a critical role for the gp130-dependent cardiomyocyte survival pathway in the transition to heart failure. In the present study, we examined plasma levels of the IL-6 family of cytokines and the soluble form of their receptors in patients with congestive heart failure (CHF). Circulating levels of the IL-6 family of cytokines, soluble IL-6 receptor (sIL-6R), and soluble gp130 (sgp130) were examined in 48 patients with various degrees of CHF, including dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and valvular cardiomyopathy (VCM). Circulating levels of IL-6, leukemia inhibitory factor (LIF), and sgp130 significantly increased in association with the severity of CHF. No significant difference was observed in the circulating levels of sIL-6R and IL-11 among these patients. Interestingly, DCM patients showed higher circulating sgp130 levels than patients with ICM or VCM. Our findings suggest that gp130 expression in the heart is likely to be dynamic, and that the IL-6 family of cytokines and their common receptor gp130 participates in the pathogenesis of CHF, especially in DCM.     

Proinflammatory cytokines in heart disease

Proinflammatory cytokines affect nearly all tissues and organ systems, and the vasculature is no exception. Although a considerable amount of research has focused on the role of the two most prominent proinflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), in the pathogenesis of sepsis and septic shock, the role of these and other cytokines in the pathogenesis of atherosclerotic lesions of the coronary artery, the acute ischemic event associated with myocardial infarction, the progression of myocardiopathies or the loss of myocardial function in congestive heart failure is a relatively recent discovery. Moreover, there has also been significant investigation of the cardioprotective effects of cytokines. Most of the attention has focused on the acute coronary syndromes and the myocardial suppression that takes place as a result of acute ischemia. The potential for anticytokine-based therapies in treating heart disease is great. Parenteral TNF-alpha neutralization and IL-1 receptor blockade are presently used to treat rheumatoid arthritis. Two orally effective agents, the IL-1beta-converting enzyme inhibitor and the mitogen-activating protein kinase p38 inhibitor, are currently being investigated in clinical trials.     

Proinflammatory cytokine levels in patients with diastolic heart failure

BACKGROUND: The role of cytokines in the pathogenesis of systolic heart failure (HF) has been well established whereas in diastolic HF it remains uncertain. AIM: To define levels of Tumor Necrosis Factor-a (TNFa) and Interleukin-6 (IL-6) in patients with diastolic HF and to reveal their association with functional class and types of left ventricular (LV) diastolic dysfunction. METHODS: We examined 26 patients with diastolic HF. The control group consisted of 10 healthy persons. Commonly used echocardiographic parameters of systolic and diastolic function of the LV, thickness of the interventricular septum (IVS), posterior LV wall thickness (PWLV), end-diastolic size of the LV (EDSLV) and left atrial (LA) volume were assessed. Serum levels of TNFa and IL-6 were measured with highly sensitive enzyme-linked immunosorbent assay. RESULTS: The TNFa and IL-6 levels were significantly higher in the group with diastolic HF than in the control group. TNFa and IL-6 levels in groups with impaired LV relaxation and restriction/pseudonormalisation were significantly higher than in the control group. TNFa level was significantly higher in the restriction/pseudonormalisation group than in the group with impaired relaxation, whereas the IL-6 level was similar. The TNFa level was significantly higher in the group with NYHA class III-IV in comparison to the group with NYHA class II. The IL-6 level in these groups was similar. Of the echocardiographic parameters, only LA volume significantly correlated with the TNF+/- level. No relationship between the IL-6 level and echocardiographic parameters was found. CONCLUSIONS: In diastolic HF, serum levels of TNFa and IL-6 are elevated. The magnitude of TNF+/- elevation is associated with the severity of HF, assessed by NYHA classification, LV diastolic dysfunction level or LA volume.