Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals.

TY - JOUR

T1 - Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals.

AU - van Hall, Gerrit

AU - Steensberg, Adam

AU - Fischer, Christian

AU - Keller, Charlotte

AU - Møller, Kirsten

AU - Moseley, Pope Lloyd

AU - Pedersen, Bente K

N1 - Keywords: Adult; Amino Acids; Humans; Interleukin-6; Male; Muscle, Skeletal; Proteins; Recombinant Proteins; Tumor Necrosis Factor-alpha

PY - 2008

Y1 - 2008

N2 - CONTEXT: IL-6 is a key modulator of immune function and suggested to be involved in skeletal muscle wasting as seen in sepsis. OBJECTIVE: Our objective was to determine the role of IL-6 in human in vivo systemic and skeletal muscle amino acid metabolism and protein turnover. SUBJECTS AND METHODS: There were 12 healthy men infused for 3 h with saline (saline, n = 6) or recombinant human IL (rhIL)-6 (n = 6). Systemic and muscle protein turnover was determined with a combination of tracer dilution methodology, primed constant infusion of L-[ring-(2)H(5)]phenylalanine, and femoral arterial-venous blood differences and m. vastus lateralis biopsies after 2-h basal, 3-h infusion, and 3 h after infusion. RESULTS: The IL-6 concentration after 30-min infusion was approximately 4 (saline) and 140 pg/ml (rhIL-6). Three-hour rhIL-6 infusion caused an approximate 50% decrease in muscle protein turnover, albeit synthesis was more suppressed than breakdown, causing a small increase in net muscle protein breakdown. Furthermore, rhIL-6 decreased arterial amino acid concentration with 20-40%, despite the increase net release from muscle. CONCLUSIONS: We demonstrated that IL-6 profoundly alters amino acid turnover. A substantial decrease in plasma amino acids was observed with a concomitant 50% decrease in muscle protein turnover, however, modest increase in net muscle degradation. We hypothesize that the profound reduction in muscle protein turnover and modest increase in net degradation are primarily caused by the reduced plasma amino acid availability and not directly mediated by IL-6.

AB - CONTEXT: IL-6 is a key modulator of immune function and suggested to be involved in skeletal muscle wasting as seen in sepsis. OBJECTIVE: Our objective was to determine the role of IL-6 in human in vivo systemic and skeletal muscle amino acid metabolism and protein turnover. SUBJECTS AND METHODS: There were 12 healthy men infused for 3 h with saline (saline, n = 6) or recombinant human IL (rhIL)-6 (n = 6). Systemic and muscle protein turnover was determined with a combination of tracer dilution methodology, primed constant infusion of L-[ring-(2)H(5)]phenylalanine, and femoral arterial-venous blood differences and m. vastus lateralis biopsies after 2-h basal, 3-h infusion, and 3 h after infusion. RESULTS: The IL-6 concentration after 30-min infusion was approximately 4 (saline) and 140 pg/ml (rhIL-6). Three-hour rhIL-6 infusion caused an approximate 50% decrease in muscle protein turnover, albeit synthesis was more suppressed than breakdown, causing a small increase in net muscle protein breakdown. Furthermore, rhIL-6 decreased arterial amino acid concentration with 20-40%, despite the increase net release from muscle. CONCLUSIONS: We demonstrated that IL-6 profoundly alters amino acid turnover. A substantial decrease in plasma amino acids was observed with a concomitant 50% decrease in muscle protein turnover, however, modest increase in net muscle degradation. We hypothesize that the profound reduction in muscle protein turnover and modest increase in net degradation are primarily caused by the reduced plasma amino acid availability and not directly mediated by IL-6.

U2 - 10.1210/jc.2007-2223

DO - 10.1210/jc.2007-2223

M3 - Journal article

C2 - 18430776

SN - 0021-972X

VL - 93

SP - 2851

EP - 2858

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 7

ER -