Mohler E R, Sorensen L C, Ghali J K, Schocken D D, Willis P W, Bowers J A, Cropp A B, Pressler M L
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
J Am Coll Cardiol. 1997 Jul;30(1):35-41. doi: 10.1016/s0735-1097(97)00145-9.
We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF).
The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown.
In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment.
The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/- SD) plasma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 were 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event-CHF or death-occurred more commonly in patients with higher IL-6 levels.
Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6.
我们试图确定氨氯地平对心力衰竭的有益作用是否可能通过降低肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平来介导。我们推测TNF-α和IL-6水平在充血性心力衰竭（CHF）患者中也可能具有预测价值。
CHF进展的分子机制可能涉及细胞因子的过度表达。氨氯地平对CHF患者细胞因子水平的影响尚不清楚。
在“前瞻性随机氨氯地平生存评估（PRAISE）”试验中，我们使用酶联免疫吸附测定法测量了92例患者的血浆TNF-α水平以及62例纽约心脏协会功能分级为III级和IV级且随机接受氨氯地平（10毫克/天）或安慰剂治疗的患者的血浆IL-6水平。在基线以及入组后8周和26周采集血样进行细胞因子检测。
基线时，氨氯地平组和安慰剂组在人口统计学和细胞因子水平方面没有差异。基线时TNF-α的平均（±标准差）血浆水平为5.69±0.32皮克/毫升，IL-6的平均血浆水平为9.23±1.26皮克/毫升。与正常受试者相比，这些水平分别升高了6倍和10倍（p<0.001）。TNF-α水平在26周期间没有显著变化（p = 0.69）。然而，与安慰剂相比，接受氨氯地平治疗的患者在26周时IL-6水平显著降低（通过Wilcoxon符号秩检验，p = 0.007）。IL-6水平较高的患者更常发生不良事件——CHF或死亡。
氨氯地平可降低CHF患者的血浆IL-6水平。氨氯地平对CHF的有益作用可能归因于细胞因子如IL-6的减少。
