title: Cytokines:  muscle protein and amino acid metabolism.
abstract: OBJECTIVE
  This review highlights the role of cytokines, in particular tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in relation to the nature of human in-vivo muscle wasting in disease.
  
  
  RESULTS
  Infusion of human TNF-α and IL-6 in healthy individuals, acutely raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle protein synthesis and breakdown, that is, reduced turnover with a minor increase in net muscle degradation. Very similar observations have been made in models of acute inflammation, induced by high-dose endotoxin injection. However, these changes were suggested not to be attributed to a direct effect of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability.
  
  
  CONCLUSIONS
  Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However, these cytokines can initiate important changes in secondary mediators and/or clinical complications that need correction therapies causing muscle wasting. Moreover, the general view from animal work is that in muscle wasting the rate of muscle protein synthesis is decreased and the rate of breakdown is increased. However, this does not seem applicable for inflammatory diseases or human models of sepsis, in which the enhanced imbalance between these two processes is observed within an enhanced, normal or reduced muscle protein turnover.
authors: Clinical Metabolomics Core Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. gvanhall@regionh.rh.dk
authors: Gerrit
authors: G
authors: van Hall
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019282:Wasting Syndrome / Q000209:etiology / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D015850:Interleukin-6; D009124:Muscle Proteins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha