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FJ
EXPRESS SUMMARY ARTICLE The Full-length version of this article is also available, published online October 29, 2001 as doi:10.1096/fj.01-0507fje. |
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2
* The Copenhagen Muscle Research Centre,
Department of Infectious Diseases, University of Copenhagen, and
The August Krogh Institute, DK-2200 Copenhagen, Denmark; and
The John B. Pierce Laboratory and Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, USA
2Correspondence: John B. Pierce Laboratory, 290 Congress Ave., New Haven, CT 06519, USA. E-mail: dneufer{at}jbpierce.org
SPECIFIC AIMS
Measurements across both working and non-working legs indicate that contracting skeletal muscle tissue is responsible for the dramatic rise in plasma interleukin 6 (IL-6) concentration during prolonged low intensity exercise. The purpose of the present study was to determine whether exercise activates transcription of the IL-6 gene in skeletal muscle and to determine the potential influence of muscle glycogen content on the IL-6 response to prolonged exercise in humans.
PRINCIPAL FINDINGS
1. Low pre-exercise muscle glycogen content in skeletal muscle elicits a greater plasma IL-6 response during prolonged exercise
To determine whether muscle glycogen content influences the regulation of IL-6 expression during prolonged exercise, six male subjects completed an exercise/diet regimen that elicited either normal (control trial) or low (
60% of normal; low glycogen trial) muscle glycogen levels. The next day, subjects performed 180 min of two-legged dynamic knee extensor exercise (50–60% of maximal work load). Before exercise, plasma concentration of IL-6 was similar in the two trials averaging 0.6 ± 0.2 ng.l-1 in the control trial and 0.7 ± 0.1 ng.l-1 in the low glycogen trial. Exercise induced a progressive rise in plasma IL-6 concentration in both trials; however, the increase occurred earlier and was much greater during the low glycogen trial (Fig. 1
). After 120 min of exercise, plasma IL-6 concentration was > twofold higher in the low glycogen trial (8.3±1.9) than in the control trial (3.8±1.1 ng.l-1) and remained significantly higher throughout the exercise period (180 min; 10.1±1.3 vs. 6.3±0.7 ng.l-1, respectively).
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2. Exercise activates expression of the IL-6 gene in skeletal muscle
To determine whether the sharp increase in plasma IL-6 concentration during exercise is mediated by activation of the IL-6 gene in muscle, IL-6 transcription and mRNA were determined by RT-PCR-based techniques on nuclei and total RNA isolated from skeletal muscle biopsies. Consistent with the low pre-exercise plasma IL-6 concentrations, transcription of the IL-6 gene was nearly undetectable before exercise. Exercise induced an increase in IL-6 transcription and mRNA content, although the timing and magnitude of the responses varied among subjects (Fig. 2
). IL-6 transcription was elevated in all subjects after 180 min of exercise.
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3. Reduced muscle glycogen concentration dramatically enhances activation of the IL-6 gene in skeletal muscle during prolonged exercise
The induction of IL-6 in skeletal muscle during exercise was dramatically elevated in all subjects when pre-exercise muscle glycogen concentration was reduced. Transcription of the IL-6 gene increased by 40-fold after 90 min and by 60-fold after 180 min of exercise, responses significantly higher than in the control trial (Fig. 2)
. IL-6 mRNA content was also significantly higher after 180 min of exercise in the low glycogen as compared with the control trial (>100-fold vs. 30-fold, respectively).
CONCLUSIONS
The results from the present study demonstrate that prolonged exercise activates transcription of the IL-6 gene in skeletal muscle of humans, a response that is dramatically enhanced under conditions in which muscle glycogen concentrations are low. Based on measurements of net IL-6 release across both the working and non-working limbs during one-legged knee extensor exercise, it has recently been established that contracting skeletal muscle tissue is the source of IL-6 production during prolonged exercise. The present study provides further evidence that induction of IL-6 expression in contracting myofibers may be largely responsible for the dramatic rise in circulating IL-6 concentration during prolonged exercise and that muscle glycogen concentration may be critical in regulating the IL-6 response to exercise.
The acute-phase response to exercise is characterized by elevations in a number of circulating proinflammatory and anti-inflammatory cytokines as well as several naturally occurring cytokine inhibitors. This integrated cytokine response has generally been considered to be induced by damage to specific contracting myofibers, similar to the acute-phase response associated with other types of tissue injury or trauma. However, during low intensity exercise that extends from 3 to 5 h, plasma IL-6 concentrations rise dramatically (10- to 25-fold) to levels comparable to that seen with severe infections. Exercise of this type (concentric, low intensity, and long duration), elicits only slight elevations in plasma creatine kinase during the subsequent 24–48 h of recovery, suggesting that production of IL-6 is not due to exercise-induced damage to skeletal muscle.
The source of IL-6 production during exercise is of obvious interest and importance. Direct evidence that contracting skeletal muscle is the major source of IL-6 production comes from a recent study in which femoral arterial and venous IL-6 concentrations and leg blood flow were determined in subjects performing one-legged low intensity knee extensor exercise for 5 h. Net IL-6 release was detected only across the exercising leg, increasing by 1000-fold over the course of the 5 h and accounting for the entire corresponding 19-fold increase in arterial plasma IL-6 concentration. Using a similar exercise model, our findings from the present study clearly demonstrate that the induction of IL-6 in exercising human skeletal muscle is mediated by transcriptional activation of the IL-6 gene and, collectively with previous data, suggest that contracting skeletal muscle tissue is the sole source of IL-6 production during exercise. Although definitive identification of the cell type(s) within muscle tissue responsible for IL-6 production during exercise will require immunolocalization studies, primary cultures of human myoblasts have been shown to actively express and secrete IL-6 in response to inflammatory stimuli, providing at least indirect evidence that contracting myofibers may be a primary source of IL-6 production during exercise.
A second major finding from the present study was that lowering muscle glycogen content before exercise enhanced the induction of IL-6 transcription and mRNA in exercising skeletal muscle. When exercise is performed at a very low intensity, the net release of IL-6 across the working muscle is fairly minimal during the initial 2 to 3 h of exercise but increases dramatically as exercise duration extends from 3 to 5 h. The fact that this latter period of exercise is also characterized by low muscle glycogen content and a decreased reliance on glycogenolysis led to the hypothesis addressed here that activation of the IL-6 gene during exercise may be sensitive to muscle glycogen content. To test this hypothesis, subjects completed identical exercise/glycogen depletion protocols on the day preceding each trial, either with or without carbohydrate replacement. The resulting 40% difference in glycogen content between trials before exercise was associated with an overall 40% greater increase in plasma IL-6 concentration (Fig. 1)
. One possibility is that differences between trials in blood-borne substrates and/or hormones may have accounted for differences in the induction of IL-6. However, this possibility was recently excluded in a related study in which subjects performed two-legged exercise with only one leg glycogen depleted before exercise. Both legs performed the same amount of work and were exposed to the same arterial substrate and hormonal milieu, yet IL-6 mRNA and protein increased more in the depleted leg. Thus, these findings suggest that glycogen content rather than circulatory factors per se may be a critical factor triggering the activation of IL-6 expression in muscle and consequent increase in plasma IL-6 concentration during exercise.
The physiological importance of IL-6 has perhaps been most well characterized with respect to liver regeneration. After hepatic injury or partial hepatectomy (2/3 removal of liver), gluconeogenic and acute-phase response genes are rapidly activated to maintain whole body metabolic homeostasis and promote tissue repair. IL-6 is considered an essential component of this process as normal liver regeneration and repair after partial hepatectomy is severely compromised in IL-6 knockout mice (-/-), but can be completely restored by injection of recombinant IL-6. In cultured hepatocytes, IL-6 stimulates glycogenolysis by simultaneously increasing glycogen phosphorylase activity and inhibiting glycogen synthase activity. IL-6 also mediates transcriptional activation of the glucose-6-phosphatase gene through a signaling system involving hepatocyte nuclear factor-1 (HNF-1)/STAT3/AP-1 interaction with the HNF-1 DNA binding site. Consistent with these data from cultured hepatocytes, infusion of recombinant human IL-6 in humans has been shown to increase hepatic glucose output. Thus, there is strong evidence indicating that IL-6 stimulates glucose production in liver. The results from the present study clearly demonstrate that the activation of IL-6 expression in muscle and a consequent rise in plasma IL-6 concentration during prolonged exercise are inversely related to glycogen content within the active muscle. Taken together, these findings support the hypothesis that IL-6 is expressed and released by contracting skeletal muscle as muscle glycogen stores decrease during prolonged exercise as a means of signaling the liver,;F3> in a counter-regulatory hormone-like manner, to accelerate glucose production (Fig. 3
).
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FOOTNOTES
1 To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.01-0507fje; to cite this article, use FASEB J. (October 29, 2001) 10.1096/fj.01-0507fje 
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|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
 |
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
A. D. Toft, L. B. Jensen, H. Bruunsgaard, T. Ibfelt, J. Halkjar-Kristensen, M. Febbraio, and B. K. Pedersen Cytokine response to eccentric exercise in young and elderly humans Am J Physiol Cell Physiol, July 1, 2002; 283(1): C289 - C295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Ronsen, T. Lea, R. Bahr, and B. K. Pedersen Enhanced plasma IL-6 and IL-1ra responses to repeated vs. single bouts of prolonged cycling in elite athletes J Appl Physiol, June 1, 2002; 92(6): 2547 - 2553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Febbraio, R. L. Starkie, S. G. Rhind, and P. N. Shek The Cellular Origin of Plasma Cytokine Expression After Acute Exercise Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1253 - R1257. [Full Text] [PDF]
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