INTERLEUKIN-6 SPILLOVER IN THE PERIPHERAL-CIRCULATION INCREASES WITH THE SEVERITY OF HEART-FAILURE, AND THE HIGH PLASMA-LEVEL OF INTERLEUKIN-6 IS AN IMPORTANT PROGNOSTIC PREDICTOR IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Objectives. We 1) evaluated whether interleukin-6 (IL-6) is produced i n the peripheral circulation in patients,vith congestive heart failure (CHF), 2) estimated the factors for increased IL-6, and 3) clarified the prognostic role of high plasma levels of IL-6 in patients with CHF . Background. Although plasma levels of IL-6 have been reported to inc rease in patients with CHF, and production of IL-6 in endothelial cell s and vascular smooth muscle cells has been postulated from in vitro s tudies, the origin of the increase of IL-6 in CHF remains unknown. Mor eover, the prognostic value of a high plasma level of IL-6, independen t of classic neurohumoral factors, remains to be elucidated. Methods. A comparison was made of the plasma levels of IL-6 between the femoral artery and the femoral vein in 13 normal subjects and in 80 patients with CHP. In another study, we measured plasma IL-6 in 100 patients wi th CHF and follow-up data. Results. Plasma IL-S levels increased signi ficantly from the femoral artery to the femoral vein in normal subject s and in patients with CHF. Arteriovenous IL-6 spillover in the leg in creased with the severity of CHF. Among the hemodynamic variables and the various neurohumoral factors, the plasma norepinephrine (NE) level shelved an independent and significant positive relation with the pla sma IL-6 level in patients with CHF. Moreover, treatment with beta-adr energic blocking agents showed an independent and significant negative relation with plasma IL-6 levels. In 100 patients, plasma IL-6 (p < 0 .0001), NE (p = 0.0004) and left ventricular ejection fraction (0.015) were significant independent prognostic predictors by Cox proportiona l hazards analysis. (C) 1998 by the American College of Cardiology.