Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats

Abstract

Background - The impact of interleukin (IL)-6 on skeletal muscle function remains the subject of controversy. Methods and Results - The effects of 7-day subcutaneous administration of recombinant human IL-6 were examined at 3 doses, 50, 100, or 250 μg·kg-1·d-1, in rats. Skeletal muscle mass decreased dose-dependently (with increasing dose: in the diaphragm, -10%, P=NS; -15%, P=0.0561; and -15% P<0.05; and in the gastrocnemius, -9%, P=NS; -9%, P=NS; and -18%, P<0.005) because of decreases in cross-sectional area of all fiber types without alterations in diaphragm contractile properties. Cardiovascular variables showed a dose-dependent heart dilatation (for end-diastolic volume: control, 78 μL; moderate dose, 123 μL; and high dose, 137 μL, P<0.001), reduced end-systolic pressure (control, 113 mm Hg; moderate dose, 87 mm Hg; and high dose, 90 mm Hg; P=0.037), and decreased myocardial contractility (for preload recruitable stroke work: control, 79 mm Hg; moderate dose, 67 mm Hg; and high dose, 48 mm Hg; P<0.001). Lung edema was confirmed by an increased wet-to-dry ratio (control, 4.2; moderate dose, 4.6; and high dose, 4.5; P<0.001) and microscopy findings. These cardiovascular alterations led to decreases in organ blood flow, particularly in the diaphragm (control, 0.56 mL·min -1·g-1; moderate dose, 0.21 mL·min -1·g-1; and high dose, 0.23 mL·min -1·g-1; P=0.037). In vitro recombinant human IL-6 administration did not cause any alterations in diaphragm force or endurance capacity. Conclusions - IL-6 clearly caused ventilatory and peripheral skeletal muscle atrophy, even after short-term administration. Blood flow redistribution, resulting from the myocardial failure induced by IL-6, was likely responsible for this muscle atrophy, because IL-6 did not exert any direct effect on the diaphragm. © 2005 American Heart Association, Inc.