Document Detail


Acute moderate elevation of TNF-alpha does not affect systemic and skeletal muscle protein turnover in healthy humans.
MedLine Citation:
PMID:  18854397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anne Marie Petersen; Peter Plomgaard; Christian P Fischer; Tobias Ibfelt; Bente Klarlund Pedersen; Gerrit van Hall
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2008-10-14
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  94     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-07     Completed Date:  2009-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  294-9     Citation Subset:  AIM; IM    
Affiliation:
The Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, DK2100 Copenhagen, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cross-Over Studies
Humans
Interleukin-6 / pharmacology
Male
Muscle Proteins / metabolism*
Muscle, Skeletal / metabolism*
Recombinant Proteins / pharmacology
Tumor Necrosis Factor-alpha / blood,  pharmacology*
Chemical
Reg. No./Substance:
0/Interleukin-6; 0/Muscle Proteins; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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