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

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 mug.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 muL; moderate dose, 123 muL; and high dose, 137 muL, 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.