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Am J Physiol Endocrinol Metab 285: E397-E402, 2003; doi:10.1152/ajpendo.00134.2003
0193-1849/03 $5.00
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Hepatosplanchnic clearance of interleukin-6 in humans during exercise

Mark A. Febbraio,1,6 Peter Ott,2 Henning Bay Nielsen,2 Adam Steensberg,1,3 Charlotte Keller,1,3 Peter Krustrup,1,5 Niels H. Secher,1,4 and Bente Klarlund Pedersen1,3

1Copenhagen Muscle Research Center and Departments of 2Hepatology, 3Infectious Diseases and 4Anesthesia, Rigshospitalet, and 5The August Krogh Institute, The University of Copenhagen, DK 2200 Copenhagen, Denmark; and 6Skeletal Muscle Research Laboratory, The School of Medical Sciences, Royal Melbourne Institute of Technology University, Bundoora, Victoria 3083, Australia

Submitted 27 March 2003 ; accepted in final form 25 April 2003

The cytokine interleukin (IL)-6 can increase markedly in the circulation during exercise, but whether the liver is a source of this increase is unknown. The aim of this study was to measure IL-6 flux across the hepatosplanchnic tissues in humans. To elevate systemic concentrations of IL-6, six healthy male subjects performed 120 min of semirecumbent cycling, and blood samples were simultaneously obtained from a brachial artery and the hepatic vein before and during exercise for the analysis of IL-6. Hepatosplanchnic blood flow (HBF) was measured using the indocyanine green infusion technique. Net hepatosplanchnic IL-6 balance was calculated from these measures. HBF was 1.3 ± 0.1 l/min at rest and was not reduced throughout exercise, averaging 1.1 ± 0.2 l/min. Arterial plasma IL-6 markedly increased (P < 0.05) from 1.8 ± 0.6 ng/l at rest to 14.3 ± 3.2 ng/l after 120 min of exercise. The hepatosplanchnic viscera did not contribute to this increase, since there was a net hepatosplanchnic IL-6 uptake (0.8 ± 0.3 vs. 5.5 ± 1.9 ng/min, rest vs. 120 min; P < 0.05). These data demonstrate that the hepatosplanchnic viscera remove IL-6 from the circulation in humans. This removal may constitute a mechanism limiting the negative chronic metabolic action of chronically elevated circulating IL-6.

liver; cytokine; metabolism; skeletal muscle contraction; blood flow



Address for reprint requests and other correspondence: M. A. Febbraio, Skeletal Muscle Research Laboratory, School of Medical Sciences, RMIT Univ., Bundoora, Victoria 3083, Australia (E-mail: mark.febbraio{at}rmit.edu.au).




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