Low IL-10/TNFα Ratio in Patients with Coronary Artery Disease and Reduced Left Ventricular Ejection Fraction with a Poor Prognosis After 10 Years
Low IL-10/TNFα Ratio in Patients with Coronary Artery Disease and Reduced Left Ventricular Ejection Fraction with a Poor Prognosis After 10 Years
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DOI：
10.1007/s10753-014-0053-5
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发表时间：
2015-04-01
期刊：
影响因子：
5.1
通讯作者：
Espinola-Klein, Christine
中科院分区：
文献类型：
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作者：
Dopheide, Joern F.;Knopf, Pascal;Espinola-Klein, Christine
单核细胞和树突状细胞（DC）在炎症过程中产生肿瘤坏死因子（TNF）α，但同时分泌白细胞介素（IL）-10以平衡促炎症。在本研究中，我们研究了 10 年后心血管预后不良的患者单核细胞和 DC 中 TNF α 和 IL-10 的表达。从 30 名患有稳定性心绞痛 (SAP) 或急性冠状动脉综合征 (ACS) 的冠状动脉疾病 (CAD) 患者中分离出外周血单核细胞。单核细胞在7天内分化为DC。通过流式细胞术分析单核细胞和 DC 中 TNF α 和 IL-10 的细胞内积累，并与心脏功能、总死亡率和心血管 (CV) 死亡率以及 10 年以上心血管事件发生率相关。我们观察到，与年龄匹配的对照组相比，SAP 和 ACS 患者的左心室功能 (LV-EF) 均下降 (p < 0.01)，单核细胞 (p = 0.01) 和 DC (p < 0.01) 的 IL-10/TNF α 比率均降低。仅单核细胞的 IL-10/TNF α 比率与 LV-EF 相关（r = 0.4302；p < 0.01）。 LV-EF 低的患者以及 IL-10/TNF α 比率低的患者在 10 年内表现出心血管死亡率增加（均 p < 0.05）。射血分数低且预后不良的患者，IL-10/TNFα比值降低。 CAD 患者心功能下降与促炎状态增加（单核细胞 IL-10/TNF α 比率低）相关。这种观察到的单核细胞中 IL-10 和 TNF α 的不平衡可能解释了动脉粥样硬化和心力衰竭的病理生理过程。
Monocytes and dendritic cells (DC) produce tumour necrosis factor (TNF)alpha during inflammatory processes, but secrete interleukin (IL)-10 simultaneously in order to balance the pro-inflammation. In the present study, we investigated the expression of TNF alpha and IL-10 by monocytes and DC in patients with a poor cardiovascular prognosis after 10 years. Peripheral blood monocytes were isolated from 30 patients with coronary artery disease (CAD) with stable angina pectoris (SAP), or with an acute coronary syndrome (ACS). Monocytes were differentiated over 7 days to DC. Intracellular accumulation of TNF alpha and IL-10 in monocytes and DC was analysed by flow cytometry and correlated with the heart function, total and cardiovascular (CV) mortality, as well as with cardiovascular event rate over 10 years. We observed a decreased left ventricular function (LV-EF) for both SAP and ACS patients (p < 0.01), as well as a reduced IL-10/TNF alpha ratio for monocytes (p = 0.01) and DC (p < 0.01) for both patient groups in comparison to age-matched control group. Only the IL-10/TNF alpha ratio for monocytes correlated with LV-EF (r = 0.4302; p < 0.01). Patients with a low LV-EF as well as patients with a low IL-10/TNF alpha ratio showed an increased cardiovascular mortality over 10 years (both p < 0.05). The IL-10/TNF alpha ratio is decreased in patients with low ejection fraction and poor prognosis. The reduced heart function correlates with an increased proinflammatory state (low monocytic IL-10/TNF alpha ratio) in patients with CAD. This observed imbalance of IL-10 and TNF alpha in monocytes might explain pathophysiological processes in atherosclerosis and heart failure.