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


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.
van Hall
Gerrit
G
Copenhagen Muscle Research Centre, Rigshospitalet, 9 Blegdamsvej, Copenhagen Ø, Denmark. gvhall@cmrc.dk
Steensberg
Adam
A
Fischer
Christian
C
Keller
Charlotte
C
Møller
Kirsten
K
Moseley
Pope
P
Pedersen
Bente K
BK
D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000596:Amino Acids; D015850:Interleukin-6; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha