Low IL-10/TNFα Ratio in Patients with Coronary Artery Disease and Reduced Left Ventricular Ejection Fraction with a Poor Prognosis After 10 Years

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.