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The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor?

Published online by Cambridge University Press:  05 March 2007

B. K. Pedersen ,
A. Steensberg ,
C. Fischer ,
C. Keller ,
P. Keller ,
P. Plomgaard ,
E. Wolsk-Petersen  and
M. Febbraio
B. K. Pedersen*
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
A. Steensberg
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
C. Fischer
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
C. Keller
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
P. Keller
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
P. Plomgaard
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
E. Wolsk-Petersen
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
M. Febbraio
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
*
*Corresponding author: Professor Bente Klarlund Pedersen, Fax: +45 35 45 76 44, Email: bkp@rh.dk
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Abstract

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For most of the last century, researchers have searched for a muscle contraction-induced factor that mediates some of the exercise effects in other tissues such as the liver and the adipose tissue. It has been called the ‘work stimulus’, the ‘work factor’ or the ‘exercise factor’. In the search for such a factor, a cytokine, IL-6, was found to be produced by contracting muscles and released into the blood. It has been demonstrated that IL-6 has many biological roles such as: (1) induction of lipolysis; (2) suppression of TNF production; (3) stimulation of cortisol production. The IL-6 gene is rapidly activated during exercise, and the activation of this gene is further enhanced when muscle glycogen content is low. In addition, carbohydrate supplementation during exercise has been shown to inhibit the release of IL-6 from contracting muscle. Thus, it is suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines could be termed ‘myokines’.

Keywords

IL-6CytokinesMuscleExerciseTraining
Type
Plenary Lecture
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 263 - 267
Copyright
Copyright © The Nutrition Society 2004

References

Febbraio, MA, Ott, P, Nielsen, HB, Steensberg, A, Keller, C, Krustrup, P, Secher, NH & Pedersen, BK (2003 a) Hepatosplanchnic clearance of interleukin-6 in humans during exercise. American Journal of Physiology 285, E397–E402.Google ScholarPubMed
Febbraio, MA & Pedersen, BK (2002) Muscle-derived interleukin-6: mechanisms for activation and possible biological roles. FASEB Journal 16, 1335–1347.CrossRefGoogle ScholarPubMed
Febbraio, MA, Steensberg, A, Keller, C, Starkie, RL, Nielsen, HB, Krustrup, P, Ott, P, Secher, NH & Pedersen, BK, (2003 b) Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. Journal of Physiology (London) 549, 607–612.CrossRefGoogle ScholarPubMed
Febbraio, MA, Steensberg, A, Starkie, RL McConell, GK & Kingwell, BA (2002) Skeletal muscle interleukin-6 and tumor necrosis factor-alpha release in healthy subjects and patients with type 2 diabetes at rest and during exercise. Metabolism 52, 939–944.CrossRefGoogle Scholar
Helge, JW, Stallknecht, B, Pedersen, BK, Galbo, H, Kiens, B & Richter, EA (2003) The effect of graded exercise on IL-6 release and glucose uptake in skeletal muscle. Journal of Physiology (London) 546, 299–305.CrossRefGoogle Scholar
Hotamisligil, GS (2000) Molecular mechanisms of insulin resistance and the role of the adipocyte. International Journal of Obesity and Related Metabolic Disorders 24, Suppl. 4, S23–S27.CrossRefGoogle ScholarPubMed
Jonsdottir, I, Schjerling, P, Ostrowski, K, Asp, S, Richter, EA & Pedersen, BK (2000) Muscle contractions induces interleukin-6 mRNA production in rat skeletal muscles. Journal of Physiology (London) 528, 157–163.CrossRefGoogle ScholarPubMed
Keller, C, Steensberg, A, Pilegaard, H, Osada, T, Saltin, B, Pedersen, BK & Neufer, PD (2001) Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB Journal 15, 2748–2750.CrossRefGoogle ScholarPubMed
Kjaer, M, Secher, NH, Bangsbo, J, Perko, G, Horn, A, Mohr, T & Galbo, H (1996) Hormonal and metabolic responses to electrically induced cycling during epidural anesthesia in humans. Journal of Applied Physiology 80, 2156–2162.CrossRefGoogle ScholarPubMed
Moldoveanu, AI, Shephard, RJ & Shek, PN (2000) Exercise elevates plasma levels but not gene expression of IL-1beta IL-6, and TNF-alpha in blood mononuclear cells. Journal of Applied Physiology 89, 1499–1504.CrossRefGoogle Scholar
Nehlsen-Canarella, SL, Fagoaga, OR & Nieman, DC (1997) Carbohydrate and the cytokine response to 2.5 hours of running. Journal of Applied Physiology 82, 1662–1667.CrossRefGoogle Scholar
Ostrowski, K, Rohde, T, Zacho, M, Asp, S & Pedersen, BK (1998) Evidence that IL-6 is produced in skeletal muscle during intense long-term muscle activity. Journal of Physiology (London) 508, 949–953.CrossRefGoogle Scholar
Pedersen, BK, Hoffman-Goetz, L (2000) Exercise and the immune system: Regulation integration and adaption. Physiological Reviews 80, 1055–1081.CrossRefGoogle Scholar
Pedersen, BK, Steensberg, A, Fischer, C, Keller, C, Keller, P, Plomgaard, P, Febbraio, M & Saltin, B (2003) Searching for the exercise factor – is IL-6 a candidate. Journal of Muscle Research and Cell Motility 24, 113–119.CrossRefGoogle ScholarPubMed
Pedersen, BK, Steensberg, A & Schjerling, P (2001) Muscle-derived interleukin-6: possible biological effects. Journal of Physiology (London) 536, 329–337.CrossRefGoogle ScholarPubMed
Penkowa, M, Keller, C, Keller, P, Jauffred, S & Pedersen, BK (2003) Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise. FASEB Journal 17, 2166–2168.CrossRefGoogle ScholarPubMed
Starkie, RL, Angus, DJ, Rolland, J, Hargreaves, M & Febbraio, M (2000) Effect of prolonged submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans. Journal of Physiology (London) 528, 647–655.CrossRefGoogle ScholarPubMed
Starkie, RL, Arkinstall, MJ, Koukoulas, I, Hawley, JA & Febbraio, MA (2001 a) Carbohydrate ingestion attenuates the increase in plasma interleukin-6, but not skeletal muscle interleukin-6 mRNA, during exercise in humans. Journal of Physiology (London) 533, 585–591.CrossRefGoogle Scholar
Starkie, RL, Ostrowski, S, Jauffred, S, Febbraio, MA & Pedersen, BK (2003) Exercise and IL-6 infusion inhibit endotoxin-induced TNF-α production in humans. FASEB Journal 17, 884–886.CrossRefGoogle ScholarPubMed
Starkie, RL, Rolland, J, Angus, DJ, Anderson, MJ & Febbraio, MA (2001 b) Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-alpha levels after prolonged running. American Journal of Physiology 280, C769–C774.CrossRefGoogle Scholar
Steensberg, A, Febbraio, MA, Osada, T, Schjerling, P, Van Hall, G, Saltin, B & Pedersen, BK (2001 a) Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. Journal of Physiology (London) 537, 633–639.CrossRefGoogle ScholarPubMed
Steensberg, A, Fischer, CP, Keller, C, Moller, K & Pedersen, BK (2003 a) IL-6 enhances plasma IL-1ra, IL-10 and cortisol in humans. American Journal of Physiology 285, E443–E437.Google ScholarPubMed
Steensberg, A, Fischer, CP, Sacchetti, M, Keller, C, Osada, T, Schjerling, P, Van Hall, G, Febbraio, MA & Pedersen, BK (2003 b) Acute interleukin-6 administration does not impair muscle glucose uptake or whole body glucose disposal in healthy humans. Journal of Physiology (London) 548, 631–638.CrossRefGoogle ScholarPubMed
Steensberg, A, Keller, C, Starkie, RL, Osada, T, Febbraio, MA & Pedersen, BK (2002) IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle. American Journal of Physiology 283, E1272–E1278.Google ScholarPubMed
Steensberg, A, Toft, AD, Schjerling, P Halkjaer-Kristensen, J & Pedersen, BK (2001 b) Plasma interleukin-6 during strenuous exercise – role of adrenaline. American Journal of Physiology 281, 1001–1004.CrossRefGoogle Scholar
Steensberg, A, Van Hall, G, Osada, T, Sacchetti, M, Saltin, B & Pedersen, BK (2000) Production of IL-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma IL-6. Journal of Physiology (London) 529, 237–242.CrossRefGoogle Scholar
Ullum, H, Haahr, PM, Diamant, M, Palmo, J, Halkjaer Kristensen, J & Pedersen, BK (1994) Bicycle exercise enhances plasma IL-6 but does not change IL-1alpha, IL-1beta, IL-6, or TNF-alpha pre-mRNA in BMNC. Journal of Applied Physiology 77, 93–97.CrossRefGoogle ScholarPubMed
Van Hall, G, Steensberg, A, Sacchetti, M, Fischer, C, Keller, C, Schjerling, P, Hiscock, N Møller, K, Saltin, B, Febbraio, MA & Pedersen, BK (2003) Interleukin-6 stimulates lipolysis and fat oxidation in humans. Journal of Clinical Endocrinology and Metabolism 88, 3005–3010.CrossRefGoogle ScholarPubMed
Wallenius, V, Wallenius, K, Ahren, B, Rudling, M, Carlsten, H, Dickson, SL, Ohlsson, C & Jansson, JO (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nature Medicine 8, 75–79.CrossRefGoogle ScholarPubMed
Winocour, PH, Durrington, PN, Bhatnagar, D, Mbewu, AD, Ishola, M, Mackness, M & Arrol, S (1992) A cross-sectional evaluation of cardiovascular risk factors in coronary heart disease associated with type 1 (insulin-dependent) diabetes mellitus. Diabetes Research and Clinical Practice 18, 173–184.CrossRefGoogle ScholarPubMed