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(Circulation. 2005;111:996-1005.)
© 2005 American Heart Association, Inc.

Heart Failure

Interleukin-6 Causes Myocardial Failure and Skeletal Muscle Atrophy in Rats

Sofie P.M. Janssen; Ghislaine Gayan-Ramirez, PhD; An Van Den Bergh; Paul Herijgers, MD, PhD; Karen Maes; Erik Verbeken, MD, PhD; Marc Decramer, MD, PhD

From the Laboratory of Pneumology (S.P.M.J., G.G.-R., K.M., M.D.), Respiratory Muscle Research Unit; the Center for Experimental Surgery and Anesthesiology (A.V.D.B., P.H.), Cardiovascular Research Unit; and the Department of Pathology (E.V.), Katholieke Universiteit Leuven, Leuven, Belgium.

Reprint requests to Prof Marc Decramer, MD, PhD, Respiratory Division, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail Marc.Decramer{at}uz.kuleuven.ac.be

Received June 21, 2004; revision received October 7, 2004; accepted November 12, 2004.

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.

Key Words: interleukins • cardiomyopathy • blood flow • contractility • muscles

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