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.


RESULTS
The effects of 7-day subcutaneous administration of recombinant human IL-6 were examined at 3 doses, 50, 100, or 250 microg x kg(-1) x 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 microL; moderate dose, 123 microL; and high dose, 137 microL, 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 x min(-1) x g(-1); moderate dose, 0.21 mL x min(-1) x g(-1); and high dose, 0.23 mL x min(-1) x 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.
Janssen
Sofie P M
SP
Laboratory of Pneumology, Respiratory Muscle Research Unit, Katholieke Universiteit Leuven, Leuven, Belgium.
Gayan-Ramirez
Ghislaine
G
Van den Bergh
An
A
Herijgers
Paul
P
Maes
Karen
K
Verbeken
Erik
E
Decramer
Marc
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D003964:Diaphragm / Q000098:blood supply / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000139:chemically induced*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000139:chemically induced*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
D015850:Interleukin-6; D011994:Recombinant Proteins