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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 586/14/3551    most recent jphysiol.2008.153551v1 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 Google Scholar Articles by Mortensen, O. H. Articles by Pedersen, B. K. PubMed PubMed Citation Articles by Mortensen, O. H. Articles by Pedersen, B. K. Related Collections Skeletal Muscle and Exercise

¹ Centre of Inflammation and Metabolism at Department of Infectious, Diseases and Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Denmark
² Department of Clinical Biochemistry, Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark

Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained at time points 0, 3 and 6 h in these individuals and in resting controls. Affymetrix microarray analysis of gene expression changes in skeletal muscle biopsies identified a small set of genes changed by IL-6 infusion. RT-PCR validation confirmed that S100A8 and S100A9 mRNA were up-regulated 3-fold in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of 50% of peak power output and arterial–femoral venous differences were obtained. Arterial plasma concentrations for calprotectin increased 2-fold compared to rest and there was a net release of calprotectin from the working muscle. In conclusion, IL-6 infusion and muscle contractions induce expression of S100A8 and S100A9 in skeletal muscle. However, IL-6 alone is not a sufficient stimulus to facilitate release of calprotectin from skeletal muscle.

(Received 6 March 2008; accepted after revision 22 May 2008; first published online 29 May 2008)
Corresponding author B. K. Pedersen: Centre of Inflammation and Metabolism, Rigshospitalet – 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Email: bkp{at}rh.dk