Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure
Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure
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DOI：
10.1016/s0735-1097(99)00495-7
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发表时间：
1999-12-01
影响因子：
24
通讯作者：
Fowler, M
中科院分区：
文献类型：
--
作者：
Gullestad, L;Aukrust, P;Fowler, M
目的探讨血管紧张素转换酶(ACE)抑制剂依那普利长期治疗对慢性充血性心力衰竭(CHF)患者各种免疫学指标的影响。血管紧张素转换酶抑制剂治疗是否会改变免疫学变量以前没有研究过。方法75名CHF患者(平均年龄52+/-11岁)随机分为低剂量(每天5 mg)和大剂量(每天40 mg)依那普利。分别于治疗前、治疗10周和治疗结束时(34周)检测免疫指标(促炎症细胞因子、趋化因子和黏附分子)的循环水平。结果CHF患者除可溶性白介素6受体外，其余免疫学指标均较正常对照组升高。在研究期间，免疫反应性IL-6水平在高剂量治疗期间降低(p<；0.05)，而可溶性IL-6受体增加(p<；0.05)，但在小剂量依那普利治疗期间没有。此外，IL-6生物活性仅在高剂量期间降低(p<；0.001)，导致两个剂量组在治疗期间的变化有显著差异(p<；0.001)。这种IL-6生物活性的降低与超声心动图测定室间隔厚度的降低显著相关(r=0.56p=0.013)。治疗期间其他变量均无变化。结论在重度CHF患者中，大剂量依那普利治疗与IL-6活性显著降低有关。然而，尽管使用了大剂量的ACE抑制剂治疗，这些患者中仍存在持续的免疫激活，这可能对CHF的进展起着重要作用。(C)1999年由美国心脏病学会颁发。
OBJECTIVES We examined the effect of long term treatment with two doses of the angiotensin converting enzyme (ACE) inhibitor enalapril on various immunological variables in patients with chronic congestive heart failure (CHF).BACKGROUND Immunological mediators are increasingly recognized to play a pathogenic role in the pathophysiology of CHF. Whether ACE inhibitor therapy modifies immunological variables has not previously been investigated.METHODS Seventy-five patients (mean age 52 +/- 11 pears) with CHF were randomized between low(5 mg daily) and high-dose (40 mg daily) enalapril in a double-blind trial. Circulating levels of immunological parameters (i.e., proinflammatory cytokines, chemokines and adhesion molecules) were measured at baseline, at 10 weeks and at the end of the study (34 weeks).RESULTS All immunological parameters, except soluble interleukin (IL)-6 receptor, were increased in CHF compared with 21 healthy controls. During the study immunoreactive IL-6 levels decreased (p < 0.05) and soluble IL-6 receptor increased (p < 0.05) during high-dose but not during low-dose enalapril therapy. Furthermore, IL-6 bioactivity decreased only during the high-dose (p < 0.001), resulting in a significant difference in change during treatment between the two dosage groups (p < 0.001). This decrease in IL-6 bioactivity was significantly associated with decreased interventricular septum thickness as assessed by echocardiography (r = 0.56, p = 0.013). No other variables changed during treatment.CONCLUSIONS In patients with severe CHF, high-dose enalapril therapy is associated with a significant decrease in IL-6 activity. However, despite treatment with a high-dose ACE inhibitor, a persistent immune activation exists in these patients which may be of importance for the progression of CHF. (C) 1999 by the American College of Cardiology.