This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Petersen, A. M. Articles by van Hall, G. Search for Related Content PubMed PubMed Citation Articles by Petersen, A. M. Articles by van Hall, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Metabolism

Acute Moderate Elevation of TNF- Does Not Affect Systemic and Skeletal Muscle Protein Turnover in Healthy Humans

The Centre of Inflammation and Metabolism, Department of Infectious Diseases (A.M.P., P.P., C.P.F., T.I., B.K.P., G.v.H.), Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, DK2100 Copenhagen, Denmark; Copenhagen Muscle Research Centre (A.M.P., P.P., C.P.F., T.I., B.K.P., G.v.H.), Rigshospitalet, DK2100 Copenhagen, Denmark; and Department of Biomedical Sciences (G.v.H.), University of Copenhagen, DK2200 Copenhagen, Denmark

Address all correspondence and requests for reprints to: G. van Hall, Rigshospitalet, Section 7652, 9 Blegdamsvej, DK-2100, Copenhagen Ø, Denmark. E-mail: gvanhall{at}cmrc.dk.

Context: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-.

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

Subjects and 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- (700 ng · m^–2 · h^–1) or 20% human albumin (control), which was the vehicle of rhTNF-. Systemic and skeletal muscle protein turnover was estimated by a combination of tracer dilution methodology (primed continuous infusion of L-[ring-²H₅]phenylalanine and L-[¹⁵N-leucine], with prime of L-[ring-²H₄]tyrosine) and femoral arterial-venous differences over the leg and muscle biopsies.

Results: Plasma TNF- concentration rapidly increased from basal levels of approximately 0.7 to 17 pg · ml^–1 with rhTNF- infusion. Whole body protein synthesis, breakdown, and net degradation were similar after the basal and infusion period of the control and rhTNF- trials. Skeletal muscle, musculus vastus lateralis, protein fractional synthetic rate was not different over 4 h of control or rhTNF- (rate of incorporation of ¹⁵N-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- infusion.

Conclusion: This study is the first to show in humans that TNF- does not affect systemic and skeletal muscle protein turnover, when acutely elevated for 4 h to moderate levels not causing adverse effects.