title: Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals.
abstract: 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.
authors.affiliation: Copenhagen Muscle Research Centre, Rigshospitalet, 9 Blegdamsvej, Copenhagen Ø, Denmark. gvhall@cmrc.dk
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
authors.forename: Adam
authors.initials: A
authors.lastname: Steensberg
authors.forename: Christian
authors.initials: C
authors.lastname: Fischer
authors.forename: Charlotte
authors.initials: C
authors.lastname: Keller
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.forename: Pope
authors.initials: P
authors.lastname: Moseley
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: 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
chemical_list: D000596:Amino Acids; D015850:Interleukin-6; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha