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J Clin Endocrinol Metab. 2009 Jan;94(1):294-9. doi: 10.1210/jc.2008-1110. Epub 2008 Oct 14.

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

Author information

1
The Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, DK2100 Copenhagen, Denmark.

Abstract

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-h recombinant human (rh) TNF-alpha infusion. We hypothesize that TNF-alpha 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-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.

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 h to moderate levels not causing adverse effects.

PMID:
18854397
DOI:
10.1210/jc.2008-1110
[Indexed for MEDLINE]

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