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

• Published in: Circulation (New York, N.Y.) Vol. 111; no. 8; pp. 996 - 1005
• Main Authors: Janssen, Sofie P.M., Gayan-Ramirez, Ghislaine, Van Den Bergh, An, Herijgers, Paul, Maes, Karen, Verbeken, Erik, Decramer, Marc
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.03.2005
• Subjects: Animals; Antihypertensive agents; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Body Weight - drug effects; Cardiology. Vascular system; Cardiomyopathies - chemically induced; Cardiovascular system; Cardiovascular System - drug effects; Cardiovascular System - physiopathology; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Diaphragm - blood supply; Diaphragm - metabolism; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Eating - drug effects; Eating - physiology; Fundamental and applied biological sciences. Psychology; Heart Failure - chemically induced; In Vitro Techniques; Interleukin-6 - administration & dosage; Interleukin-6 - blood; Interleukin-6 - pharmacology; Liver - blood supply; Liver - metabolism; Lung - blood supply; Lung - metabolism; Male; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Skeletal - blood supply; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiopathology; Muscular Atrophy - chemically induced; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardium - pathology; Organ Size - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Vertebrates: cardiovascular system; Rat; Cardiomyopathy; Cytokine; Rodentia; Contractility; Cardiovascular disease; Striated muscle; Myocardial disease; Blood flow; interleukins; Atrophy; Interleukin 6; Vertebrata; Mammalia; muscles; Heart disease; Animal; Hemodynamics
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000156469.96135.0D

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.