Department of Internal Medicine II, Universitätsmedizin of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany,
Inflammation. 2015 Apr;38(2):911-22. doi: 10.1007/s10753-014-0053-5.
Monocytes and dendritic cells (DC) produce tumour necrosis factor (TNF)α 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 TNFα 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 TNFα 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/TNFα 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/TNFα 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/TNFα ratio showed an increased cardiovascular mortality over 10 years (both p<0.05). The IL-10/TNFα 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/TNFα ratio) in patients with CAD. This observed imbalance of IL-10 and TNFα in monocytes might explain pathophysiological processes in atherosclerosis and heart failure.
在炎症过程中,单核细胞和树突状细胞 (DC) 会产生肿瘤坏死因子 (TNF)α,但同时也会分泌白细胞介素 (IL)-10 以平衡促炎状态。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 TNFα 和 IL-10 的表达。从 30 例稳定性心绞痛 (SAP) 或急性冠状动脉综合征 (ACS) 的冠心病 (CAD) 患者中分离外周血单核细胞。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 TNFα 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 年内心血管事件发生率相关。我们观察到 SAP 和 ACS 患者的左心室功能 (LV-EF) 降低(均为 p<0.01),以及两组患者单核细胞和 DC 的 IL-10/TNFα 比值降低(均为 p<0.01)与年龄匹配的对照组相比。只有单核细胞的 IL-10/TNFα 比值与 LV-EF 相关(r=0.4302;p<0.01)。LV-EF 低的患者和 IL-10/TNFα 比值低的患者在 10 年内心血管死亡率增加(均为 p<0.05)。IL-10/TNFα 比值降低与 CAD 患者射血分数降低和预后不良相关。单核细胞中观察到的 IL-10 和 TNFα 失衡可能解释了动脉粥样硬化和心力衰竭的病理生理过程。