Acute moderate elevation of TNF-alpha does not affect systemic and skeletal muscle protein turnover in healthy humans.
BACKGROUND
Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha.


OBJECTIVE
In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover via a 4-h recombinant human (rh) TNF-alpha infusion. We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibits synthesis.


METHODS
Using a randomized, controlled, crossover design, postabsorptive healthy young males (n = 8) were studied 2 h under basal conditions followed by a 4-h infusion of either rhTNF-alpha (700 ng . m(-2) . h(-1)) or 20% human albumin (control), which was the vehicle of rhTNF-alpha. Systemic and skeletal muscle protein turnover was estimated by a combination of tracer dilution methodology (primed continuous infusion of l-[ring-(2)H(5)]phenylalanine and l-[(15)N-leucine], with prime of l-[ring-(2)H(4)]tyrosine) and femoral arterial-venous differences over the leg and muscle biopsies.


RESULTS
Plasma TNF-alpha concentration rapidly increased from basal levels of approximately 0.7 to 17 pg . ml(-1) with rhTNF-alpha infusion. Whole body protein synthesis, breakdown, and net degradation were similar after the basal and infusion period of the control and rhTNF-alpha trials. Skeletal muscle, musculus vastus lateralis, protein fractional synthetic rate was not different over 4 h of control or rhTNF-alpha (rate of incorporation of (15)N-leucine). Muscle protein turnover determined with the phenylalanine three-compartment model showed similar muscle synthesis, breakdown, and net muscle degradation after 2-h basal and after 4-h control or rhTNF-alpha infusion.


CONCLUSIONS
This study is the first to show in humans that TNF-alpha does not affect systemic and skeletal muscle protein turnover, when acutely elevated for 4 h to moderate levels not causing adverse effects.
The Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, DK2100 Copenhagen, Denmark.
Anne Marie
AM
Petersen
Peter
P
Plomgaard
Christian P
CP
Fischer
Tobias
T
Ibfelt
Bente Klarlund
BK
Pedersen
Gerrit
G
van Hall
D000328:Adult; D018592:Cross-Over Studies; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000494:pharmacology*
D015850:Interleukin-6; D009124:Muscle Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha