Muscle‐derived interleukin‐6: possible biological effects
Open accessAbstract
Interleukin‐6 (IL‐6) is produced locally in working skeletal muscle and can account for the increase in plasma IL‐6 during exercise. The production of IL‐6 during exercise is related to the intensity and duration of the exercise, and low muscle glycogen content stimulates the production. Muscle‐derived IL‐6 is released into the circulation during exercise in high amounts and is likely to work in a hormone‐like fashion, exerting an effect on the liver and adipose tissue, thereby contributing to the maintenance of glucose homeostasis during exercise and mediating exercise‐induced lipolysis. Muscle‐derived IL‐6 may also work to inhibit the effects of pro‐inflammatory cytokines such as tumour necrosis factor α. The latter cytokine is produced by adipose tissue and inflammatory cells and appears to play a pathogenetic role in insulin resistance and atherogenesis.
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Interleukin-6 is produced in, and subsequently released from, contracting muscle.
“However, there is also evidence that interleukin-6 is produced in, and subsequently released from, contracting muscle (61,62)”
From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [61]
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Self-citationFranchimont, N., Gangji, V., Durant, D., & CANALIS, E. M. (1997) · Endocrinology · doi:10.1210/endo.138.12.5559 · Cited by 49 · see citing works
Glucoregulation during and after intense exercise: Effects of α-adrenergic blockade
Sigal, R. J., Fisher, S. J., Manzon, A., Morais, J. A., Halter, J. B., Vranić, M., & Marliss, E. B. (2000) · Metabolism · doi:10.1016/s0026-0495(00)90374-3 · Cited by 48 · see citing works
Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia.
Saito, H., Patterson, C., Hu, Z., Runge, M. S., Tipnis, U. R., Sinha, M., & Papaconstantinou, J. (2000) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.5.h2241 · Cited by 42 · see citing works
Effects of calcitonin gene-related peptide and interleukin 6 on myoblast differentiation
Okazaki, S., Kawai, H., Arii, Y., Yamaguchi, H., & Saito, S. (1996) · Cell Proliferation · doi:10.1046/j.1365-2184.1996.00996.x · Cited by 28 · see citing works
Necrotizing myopathy induced by overexpression of interferon-? in transgenic mice
Shelton, G. D., Calcutt, N. A., Garrett, R. S., Gu, D., Sarvetnick, N., Campana, W. M., & Powell, H. C. (1999) · Muscle & Nerve · doi:10.1002/(sici)1097-4598(199902)22:2 · Cited by 24 · see citing works
Lack of IL-6 production during exercise in patients with mitochondrial myopathy
Steensberg, A., Vissing, J., & Pedersen, B. K. (2001) · European Journal of Applied Physiology · doi:10.1007/s004210000351 · Cited by 12 · see citing works
Self-citationInterleukin-6 receptor shedding: a possible role for members of the ADAM family
Croucher, P. I., Wang, F., & Hargreaves, P. G. (1999) · Biochemical Society Transactions · doi:10.1042/bst0270224 · Cited by 9 · see citing works
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Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases
Pedersen, B. K., & Saltin, B. (2015) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12581 · Cited by 3,514 · see citing works
Self-citationThe anti-inflammatory effect of exercise
Petersen, A. M. W., & Pedersen, B. K. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00164.2004 · Cited by 3,100 · see citing works
Self-citationMuscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388 · see citing works
Self-citationEvidence for prescribing exercise as therapy in chronic disease
Pedersen, B. K., & Saltin, B. (2006) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/j.1600-0838.2006.00520.x · Cited by 1,384 · see citing works
Self-citationInterleukin-6-deficient mice develop mature-onset obesity
Wallenius, V., Wallenius, K., Ahrén, B., Rudling, M., Carlsten, H., Dickson, S. L., Ohlsson, C., & Jansson, J.-O. (2002) · Nature Medicine · doi:10.1038/nm0102-75 · Cited by 1,213 · see citing works
The Effects of Physical Activity on Serum C-Reactive Protein and Inflammatory Markers
Kasapis, C., & Thompson, P. D. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.12.077 · Cited by 1,149 · see citing works
IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans
Steensberg, A., Fischer, C. P., Keller, C., Møller, K., & Pedersen, B. K. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00074.2003 · Cited by 1,135 · see citing works
Self-citationInsulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
Fernández-Real, J. M., & Ricart, W. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0010 · Cited by 886 · see citing works
Interleukin-6 induces cellular insulin resistance in hepatocytes.
Senn, J. J., Klover, P. J., Nowak, I. A., & Mooney, R. A. (2002) · Diabetes · doi:10.2337/diabetes.51.12.3391 · Cited by 883 · see citing works
Muscle‐derived interleukin‐6: mechanisms for activation and possible biological roles
FEBBRAIO, M. A., & PEDERSEN, B. K. (2002) · The FASEB Journal · doi:10.1096/fj.01-0876rev · Cited by 875 · see citing works
Self-citationRole of Myokines in Exercise and Metabolism
Pedersen, B. K., Åkerström, T. C. A., Nielsen, A. R., & Fischer, C. P. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00080.2007 · Cited by 841 · see citing works
Self-citationExercise and IL‐6 infusion inhibit endotoxin‐induced TNF‐α production in humans
Starkie, R., Ostrowski, S. R., Jauffred, S., Febbraio, M., & Pedersen, B. K. (2003) · The FASEB Journal · doi:10.1096/fj.02-0670fje · Cited by 790 · see citing works
Self-citationAge-related inflammatory cytokines and disease
Brüünsgaard, H., & Pedersen, B. K. (2003) · Immunology and Allergy Clinics of North America · doi:10.1016/s0889-8561(02)00056-5 · Cited by 608 · see citing works
Self-citationThe role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance
Goossens, G. H. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.10.010 · Cited by 591 · see citing works
Searching for the exercise factor: is IL-6 a candidate?
Pedersen (2003) · Journal of Muscle Research and Cell Motility · doi:10.1023/a:1026070911202 · Cited by 564 · see citing works
Pedersen, B. K. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120033 · Cited by 516 · see citing works
Self-citationThe selfish brain: Competition for energy resources
Peters, A., Schweiger, U., Pellerin, L., Hubold, C., Oltmanns, K. M., Conrad, M., Schultes, B., Born, J., & Fehm, H. L. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.03.002 · Cited by 489 · see citing works
Interleukin-6 Is a Novel Factor Mediating Glucose Homeostasis During Skeletal Muscle Contraction
Febbraio, M. A., Hiscock, N., Sacchetti, M., Fischer, C. P., & Pedersen, B. K. (2004) · Diabetes · doi:10.2337/diabetes.53.7.1643 · Cited by 455 · see citing works
Self-citationIL-6 and TNF-α expression in, and release from, contracting human skeletal muscle
Steensberg, A., Keller, C., Starkie, R. L., Osada, T., Febbraio, M. A., & Pedersen, B. K. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00255.2002 · Cited by 410 · see citing works
Self-citationCerebral perturbations provoked by prolonged exercise
Nybo, L., & Secher, N. H. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.03.005 · Cited by 398 · see citing works
An immune origin of type 2 diabetes?
Kolb, H., & Mandrup-Poulsen, T. (2005) · Diabetologia · doi:10.1007/s00125-005-1764-9 · Cited by 394 · see citing works
Brower, R. G. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181b6e30a · Cited by 387 · see citing works
Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle
Bach, D., Naon, D., Pich, S., Soriano, F. X., Vega, N., Rieusset, J., Laville, M., Guillet, C., Boirie, Y., Wallberg-Henriksson, H., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2685 · Cited by 369 · see citing works
Tissue homeostasis and inflammation
Meizlish, M. L., Franklin, R. A., Zhou, X., & Medzhitov, R. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053734 · Cited by 364 · see citing works
The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control
Pedersen, B. K. (2006) · Essays in Biochemistry · doi:10.1042/bse0420105 · Cited by 349 · see citing works
Self-citationReza, M. M., Subramaniyam, N., Sim, C. M., Ge, X., Sathiakumar, D., McFarlane, C., Sharma, M., & Kambadur, R. (2017) · Nature Communications · doi:10.1038/s41467-017-01131-0 · Cited by 335 · see citing works
AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise.
Kelly, M., Keller, C., Avilucea, P. R., Keller, P., Luo, Z., Xiang, X., Giralt, M., Hidalgo, J., Saha, A. K., Pedersen, B. K., et al. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.188 · Cited by 289 · see citing works
Self-citationDiabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients
Saraheimo, M., Teppo, A.-M., Forsblom, C., Fagerudd, J., & Groop, P.-H. (2003) · Diabetologia · doi:10.1007/s00125-003-1194-5 · Cited by 255 · see citing works
Skeletal Muscle Wasting and Renewal: A Pivotal Role of Myokine IL-6
Belizário, J. E., Fontes-Oliveira, C. C., Borges, J. P., Kashiabara, J. A., & Vannier, E. (2016) · SpringerPlus · doi:10.1186/s40064-016-2197-2 · Cited by 244 · see citing works
Pedersen, B. K., & Febbraio, M. (2005) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.04.008 · Cited by 233 · see citing works
Self-citationMuscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects
Pedersen, B. K., Steensberg, A., Keller, P., Keller, C., Fischer, C., Hiscock, N., van Hall, G., Plomgaard, P., & Febbraio, M. A. (2003) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-002-0981-z · Cited by 228 · see citing works
Self-citationMetabolic adaptation in obesity and type ii diabetes: myokines, adipokines and hepatokines
Oh, K.-J., Lee, D., Kim, W., Han, B., Lee, S., & Bae, K.-H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010008 · Cited by 210 · see citing works
Physical Activity and Cancer Prevention: Pathways and Targets for Intervention
Rogers, C. J., Colbert, L. H., Greiner, J. W., Perkins, S. N., & Hursting, S. D. (2008) · Sports Medicine · doi:10.2165/00007256-200838040-00002 · Cited by 170 · see citing works
Fischer, C. P., Plomgaard, P., Hansen, A. K., Pilegaard, H., Saltin, B., & Pedersen, B. K. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00206.2004 · Cited by 165 · see citing works
Self-citationFox, J., Rioux, B. V., Goulet, E. D. B., Johanssen, N. M., Swift, D. L., Bouchard, D. R., Loewen, H., & Sénéchal, M. (2018) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12904 · Cited by 161 · see citing works
Interleukin‐6 production in human subcutaneous abdominal adipose tissue: the effect of exercise
Lyngsø, D., Simonsen, L., & Bülow, J. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.019380 · Cited by 155 · see citing works
The role of extracellular vesicles in skeletal muscle and systematic adaptation to exercise
Vechetti, I. J., Valentino, T., Mobley, C. B., & McCarthy, J. J. (2021) · The Journal of Physiology · doi:10.1113/jp278929 · Cited by 141 · see citing works
ERK2 is required for efficient terminal differentiation of skeletal myoblasts
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Interleukin-6 release from human skeletal muscle during exercise: relation to AMPK activity
MacDonald, C., Wojtaszewski, J. F. P., Pedersen, B. K., Kiens, B., & Richter, E. A. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00242.2003 · Cited by 105 · see citing works
Self-citationBiochemical changes in response to intensive resistance exercise training in the elderly
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Acute myotube protein synthesis regulation by IL-6-related cytokines
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- Authors
- Pedersen, B. K., Steensberg, A., & Schjerling, P.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Pedersen, Bente Klarlund
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2001-10
- Volume
- 536
- Issue
- 2
- Pages
- 329-337
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2278876
- OpenAlex
- W2149631937
- Cited by
- 599
- References
- 98
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 13 · 2023: 27 · 2022: 38 · 2021: 38 · 2020: 29 · 2019: 22 · 2018: 34 · 2017: 31 · 2016: 22 · 2015: 29 · 2014: 25 · 2013: 25 · 2012: 23
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- interleukin-6, skeletal muscle, physical activity, muscle glycogen, glucose homeostasis, TNF-α, insulin resistance, atherogenesis, adipose tissue, inflammatory cytokines
- MeSH terms
- Physical Exertion, Humans, Interleukin-6, Muscle, Skeletal
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