Acute moderate elevation of TNF-{alpha} does not affect systemic and skeletal muscle protein turnover in healthy humans.

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Context: 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 hours recombinant human TNF-alpha infusion (rhTNF-alpha). We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibit synthesis. Subjects and Methods: Using a randomized controlled, crossover design post-absorptive healthy young males (n=8) were studied 2 hours under basal conditions followed by 4 hours 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 were estimated by a combination of tracer dilution methodology (primed continuous infusion of L-[ring-(2)H5]phenylalanine and L-[(15)N-leucine], with prime of L-[ring-(2)H4]tyrosine), 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, m. vastus lateralis, protein fractional synthetic rate was not different over 4 hours of Control or rhTNF-alpha (rate of incorporation of (15)N-leucine). Muscle protein turnover determined with the phenylalanine 3-compartment model showed similar muscle synthesis, breakdown and net muscle degradation after 2 hours basal and after 4 hours Control or rhTNF-alpha infusion. Conclusion: 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 hours to moderate levels not causing adverse effects.
TidsskriftJournal of Clinical Endocrinology and Metabolism
Sider (fra-til)294-299
Antal sider6
StatusUdgivet - 2009

ID: 8442332