Searching for the exercise factor: is IL-6 a candidate?

Pedersen

doi:10.1023/a:1026070911202

Cited by 567Exercise and Physiological ResponsesAdipokines, Inflammation, and Metabolic DiseasesMuscle Physiology and Disorders

Searching for the exercise factor: is IL-6 a candidate?

Pedersen·2003·Journal of Muscle Research and Cell Motility

DOI 10.1023/a:1026070911202

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Abstract

For years the search for the stimulus that initiates and maintains the change of excitability or sensibility of the regulating centers in exercise has been progressing. For lack of more precise knowledge, it has been called the 'work stimulus', 'the work factor' or 'the exercise factor'. In other terms, one big challenge for muscle and exercise physiologists has been to determine how muscles signal to central and peripheral organs. Here we discuss the possibility that interleukin-6 (IL-6) could mediate some of the health beneficial effects of exercise. In resting muscle, the IL-6 gene is silent, but it is rapidly activated by contractions. The transcription rate is very fast and the fold changes of IL-6 mRNA is marked. IL-6 is released from working muscles into the circulation in high amounts. The IL-6 production is modulated by the glycogen content in muscles, and IL-6 thus works as an energy sensor. IL-6 exerts its effect on adipose tissue, inducing lipolysis and gene transcription in abdominal subcutaneous fat and increases whole body lipid oxidation. Furthermore, IL-6 inhibits low-grade TNF-alpha-production and may thereby inhibit TNF-alpha-induced insulin resistance and atherosclerosis development. We propose that IL-6 and other cytokines, which are produced and released by skeletal muscles, exerting their effects in other organs of the body, should be named 'myokines'.

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The concept of 'exercise factor' was based on the fact that muscle contractions engage metabolic and physiological responses in other organs, and that these are not mediated by the nervous system.
“The concept of “exercise factor” was based on the fact that muscle contractions engage metabolic and physiological responses in other organs, and that these are not mediated by the nervous system (Pedersen et al., 2003).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Pedersen et al., 2003
Skeletal muscle is an active endocrine organ capable of synthesizing and releasing myokines in response to exercise stimulation.
“skeletal muscle has been re-recognized as an active endocrine organ capable of synthesizing and releasing a series of bioactive molecules in response to exercise stimulation, known as “myokines”.”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [6]
Pedersen et al. in 2003 first demonstrated that skeletal muscle could synthesize and release large amounts of interleukin-6 into the circulation during exercise, thereby regulating the metabolism and function of distant organs.
“The discovery of myokines stemmed from the work of Pedersen et al. in 2003, who first demonstrated that skeletal muscle could synthesize and release large amounts of interleukin-6 (IL-6) into the circulation during exercise, thereby regulating the metabolism and function of distant organs [6].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [6]
In healthy and hyperlipidaemic adults, supplementation with 3.6 g/d EPA and DHA for up to 6 weeks did not affect sICAM-1 or sVCAM-1.
“¼ sICAM-1, sVCAM-1”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [618]
In healthy and hyperlipidaemic adults, supplementation with 3.6 g/d EPA and DHA for up to 6 weeks inversely affected sE-selectin.
“# sE-selectin”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [618]

IL-6 production is upregulated by muscle contraction and IL-6 may be released from contracting skeletal muscle.
“it is now clear that IL-6 [7] and IL-8 [8] production is upregulated by muscle contraction and that these cytokines may be released from contracting skeletal muscle.”
From Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase (2009) · cites this paper as [8]
IL-6 is produced and released by contracting skeletal muscle fibres and exerts effects in other organs of the body.
“Recently, IL-6 was introduced as the first myokine, defined as a cytokine, which is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body.”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [18]
Skeletal muscle is an endocrine organ.
“We suggest that skeletal muscle is an endocrine organ and that myokines may be involved in mediating the beneficial effects against CNCDs associated with low-grade inflammation.”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [18]
Skeletal muscle produces and releases cytokines, also called myokines.
“skeletal muscle has recently been identified as an endocrine organ, which produces and releases cytokines (also called myokines) [18, 19].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [18]
Working muscle produces IL-6.
“A number of studies have demonstrated that working muscle produces IL-6.”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [18]
Muscle biopsies before and after exercise in humans and rats demonstrate very little IL-6 mRNA in resting muscle, but up to a 100-fold increase in exercising skeletal muscle.
“Thus muscle biopsies obtained before and after exercise in humans and rats demonstrate very little IL-6 mRNA in resting muscle, but up to a 100-fold increase in exercising skeletal muscle [18, 64, 65].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [18]
The magnitude by which plasma IL-6 increases is related to exercise duration, intensity, and muscle mass involved in the mechanical work.
“The magnitude by which plasma IL-6 increases is related to exercise duration, intensity, and muscle mass involved in the mechanical work [13, 18, 60, 62].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [18]

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No excess 12-year mortality in men with impaired glucose tolerance who participated in the Malm� Preventive Trial with diet and exercise
Eriksson, K.-F., & Lindg�rde, F. (1998) · Diabetologia · doi:10.1007/s001250051024 · Cited by 184 · see citing works
GLUT 4 and insulin receptor binding and kinase activity in trained human muscle.
Dela, F., Handberg, A., Mikines, K. J., Vinten, J., & Galbo, H. (1993) · The Journal of Physiology · doi:10.1113/jphysiol.1993.sp019833 · Cited by 170 · see citing works
Relationship between serum tumor necrosis factor-α and insulin resistance in obese men with Type 2 diabetes mellitus
Mishima, Y., Kuyama, A., Tada, A., Takahashi, K., Ishioka, T., & Kibata, M. (2001) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(00)00247-3 · Cited by 159 · 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
Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans
Steensberg, A., Fischer, C. P., Sacchetti, M., Keller, C., Osada, T., Schjerling, P., van Hall, G., Febbraio, M. A., & Pedersen, B. K. (2003) · The Journal of Physiology · doi:10.1111/j.1469-7793.2003.00631.x · Cited by 152 · see citing works
Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans
Steensberg, A., Fischer, C. P., Sacchetti, M., Keller, C., Osada, T., Schjerling, P., van Hall, G., Febbraio, M. A., & Pedersen, B. K. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.032938 · Cited by 152 · see citing works
Human Breast Adipocytes Express Interleukin-6 (IL-6) and Its Receptor System: Increased IL-6 Production by β-Adrenergic Activation and Effects of IL-6 on Adipocyte Function
Päth, G., Bornstein, S. R., Gurniak, M., Chrousos, G. P., Scherbaum, W. A., & Hauner, H. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.5.7494 · Cited by 150 · see citing works
Chemokines are elevated in plasma after strenuous exercise in humans
Ostrowski, K., Rohde, T., Asp, S., Schjerling, P., & Pedersen, B. K. (2001) · European Journal of Applied Physiology · doi:10.1007/s004210170012 · Cited by 146 · see citing works
Plasma interleukin-6 during strenuous exercise: role of epinephrine
Steensberg, A., Toft, A. D., Schjerling, P., Halkjær-Kristensen, J., & Pedersen, B. K. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.3.c1001 · Cited by 137 · see citing works
Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice
Matthys, P., Mitera, T., Heremans, H., Van Damme, J., & Billiau, A. (1995) · Infection and Immunity · doi:10.1128/iai.63.4.1158-1164.1995 · Cited by 134 · see citing works
Effect of prolonged, submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans
Starkie, R. L., Angus, D. J., Rolland, J. M., Hargreaves, M., & Febbraio, M. A. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00647.x · Cited by 131 · see citing works
The Cytokine Response to Strenuous Exercise
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Effects of mode and carbohydrate on the granulocyte and monocyte response to intensive, prolonged exercise
Nieman, D. C., Nehlsen‐Cannarella, S. L., Fagoaga, O. R., Henson, D. A., Utter, A. C., Davis, J. M., Williams, F. E., & Butterworth, D. E. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.84.4.1252 · Cited by 124 · see citing works
Modification of immune responses to exercise by carbohydrate, glutamine and anti‐oxidant supplements
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Intracellular monocyte and serum cytokine expression is modulated by exhausting exercise and cold exposure
Rhind, S. G., Castellani, J. W., Brenner, I., Shephard, R. J., Zamecnik, J., Montain, S. J., Young, A., & Shek, P. N. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.1.r66 · Cited by 112 · see citing works
N-3 polyunsaturated fatty acids do not affect cytokine response to strenuous exercise
Toft, A. D., Thorn, M., Ostrowski, K., Asp, S., Møller, K., Iversen, S. A., Hermann, C., Søndergaard, S. R., & Pedersen, B. K. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.6.2401 · Cited by 106 · see citing works
Exercise training and heart failure: a systematic review of current evidence.
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Lymphocytes and NK cell activity during repeated bouts of maximal exercise
Nielsen, H. B., Secher, N. H., Christensen, N. J., & Pedersen, B. K. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.271.1.r222 · Cited by 97 · see citing works
Prolonged submaximal eccentric exercise is associated with increased levels of plasma IL-6
Rohde, T., MacLean, D. A., Richter, E. A., Kiens, B., & Pedersen, B. K. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.1.e85 · Cited by 92 · see citing works
Hormonal and metabolic responses to electrically induced cycling during epidural anesthesia in humans
Kjaer, M., Secher, N. H., Bangsbo, J., Perko, G., Horn, A., Mohr, T., & Galbo, H. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.80.6.2156 · Cited by 53 · cited 1× · see citing works
“…muscles to other organs are not the nervous system as electrical stimulation of paralysed muscles in spinal cord injured patients, with no afferent and efferent nerve impulses, induces in essence the same physiological changes as in intact human beings (Kjaer et al., 1996; Mohr et al., 1997).”
Background
FAMILIAL AGGREGATION OF CARDIOVASCULAR RESPONSE TO SUBMAXIMAL EXERCISE IN THE HERITAGE FAMILY STUDY
Leon, A. S., An, P., Rice, T., russe, L. P., Gagnon, J., Wilmore, J. H., Skinner, J. S., Rao, D. C., & Bouchard, C. (2001) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200105001-01173 · Cited by 43 · see citing works
Inverse melting of metastable Nb–Cr solid solutions
Michaelsen, C., Sinkler, W. A., Pfullmann, T., & Bormann, R. (1996) · Journal of Applied Physics · doi:10.1063/1.363048 · Cited by 35 · see citing works
A cross-sectional evaluation of cardiovascular risk factors in coronary heart disease associated with Type 1 (insulin-dependent) diabetes mellitus
Winocour, P. H., Durrington, P. N., Bhatnagar, D., Mbewu, A. D., Ishola, M., Mackness, M., & Arrol, S. (1992) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(92)90143-f · Cited by 33 · 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

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Sorted by citations

The pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212 · see citing works
The 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
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · see citing works
Muscle 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
The Metabolic Syndrome
Cornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0024 · Cited by 2,162 · see citing works
Adipose Tissue, Inflammation, and Cardiovascular Disease
Berg, A. H., & Scherer, P. E. (2005) · Circulation Research · doi:10.1161/01.res.0000163635.62927.34 · Cited by 2,113 · see citing works
A comprehensive review on metabolic syndrome
Kaur, J. (2014) · Cardiology Research and Practice · doi:10.1155/2014/943162 · Cited by 1,889 · see citing works
Retracted
Muscle–Organ Crosstalk: The Emerging Roles of Myokines
Severinsen, M. C. K., & Pedersen, B. K. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa016 · Cited by 1,226 · see citing works
“596 Endocrine Reviews, August 2020, 41(4):594–609 Severinsen and Pedersen Myokines in Muscle–Organ Crosstalk in myostatin knockout mice, cattle, sheep, and dogs (43-45) that demonstrate an increase in fiber cross-sectional area and in fiber number.”
BackgroundInfluential
The Metabolic Syndrome
Grundy, S. M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-5839-6_1 · Cited by 1,225 · see citing works
Integrative Biology of Exercise
Hawley, J. A., Hargreaves, M., Joyner, M. J., & Zierath, J. R. (2014) · Cell · doi:10.1016/j.cell.2014.10.029 · Cited by 1,152 · see citing works
Dietary factors and low-grade inflammation in relation to overweight and obesity
Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., Esposito, K., Jönsson, L. S., Kolb, H., Lansink, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114511005460 · Cited by 1,098 · see citing works
Neurobiology of exercise
Dishman, R. K., Berthoud, H., Booth, F. W., Cotman, C. W., Edgerton, V. R., Fleshner, M. R., Gandevia, S. C., Gomez‐Pinilla, F., Greenwood, B. N., Hillman, C. H., et al. (2006) · Obesity · doi:10.1038/oby.2006.46 · Cited by 958 · see citing works
Role 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
Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase
Matthews, V. B., Åström, M.-B., Chan, M. H. S., Bruce, C. R., Krabbe, K. S., Prelovsek, O., Åkerström, T., Yfanti, C., Broholm, C., Mortensen, O. H., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1364-1 · Cited by 722 · see citing works
Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms
Booth, F. W., Roberts, C. K., Thyfault, J. P., Ruegsegger, G. N., & Toedebusch, R. G. (2017) · Physiological Reviews · doi:10.1152/physrev.00019.2016 · Cited by 696 · see citing works
Release of Interleukins and Other Inflammatory Cytokines by Human Adipose Tissue Is Enhanced in Obesity and Primarily due to the Nonfat Cells
Fain, J. N. (2006) · Vitamins and hormones · doi:10.1016/s0083-6729(06)74018-3 · Cited by 679 · see citing works
IL-6-induced skeletal muscle atrophy
Haddad, F., Zaldivar, F., Cooper, D. M., & Adams, G. R. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01026.2004 · Cited by 612 · see citing works
Muscle as a secretory organ
Pedersen, B. K. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120033 · Cited by 516 · see citing works
Exercise as a Mean to Control Low‐Grade Systemic Inflammation
Mathur, N., & Pedersen, B. K. (2008) · Mediators of Inflammation · doi:10.1155/2008/109502 · Cited by 514 · see citing works
Central Fatigue
MEEUSEN, R. R., Watson, P., Hasegawa, H., Roelands, B., & Piacentini, M. F. (2006) · Sports Medicine · doi:10.2165/00007256-200636100-00006 · Cited by 488 · see citing works
Exercise as an anti-inflammatory therapy for rheumatic diseases—Myokine regulation
Benatti, F. B., & Pedersen, B. K. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.193 · Cited by 474 · see citing works
Prevention of Atrial Fibrillation
Benjamin, E. J., Chen, P., Bild, D. E., Mascette, A. M., Albert, C. M., Alonso, Á., Calkins, H. G., Connolly, S. J., Curtis, A. B., Darbar, D., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.825380 · Cited by 471 · see citing works
Lower circulating irisin is associated with type 2 diabetes mellitus
Liu, J., Wong, M. D. S., Toy, W. C., Tan, C., Liu, S., Ng, X. W., Subramaniam, T., Sum, C. F., & Lim, S. C. (2013) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2013.03.002 · Cited by 446 · see citing works
Exercise and metabolic health: beyond skeletal muscle
Thyfault, J., & Bergouignan, A. (2020) · Diabetologia · doi:10.1007/s00125-020-05177-6 · Cited by 373 · see citing works
Role of Myokines in Regulating Skeletal Muscle Mass and Function
Lee, J. H., & Jun, H.-S. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00042 · Cited by 432 · see citing works
Physical activity and modulation of systemic low-level inflammation
Bruunsgaard, H. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0505247 · Cited by 429 · 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
Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations
Hoffmann, C., & Weigert, C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029793 · Cited by 393 · see citing works
Consequences of bed rest
Brower, R. G. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181b6e30a · Cited by 387 · see citing works
Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases
Leal, L. G., Lopes, M. A., & Batista, M. L. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01307 · Cited by 382 · see citing works
Inflammation and Skeletal Muscle Wasting During Cachexia
Webster, J. M., Kempen, L. J. A. P., Hardy, R. S., & Langen, R. C. J. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.597675 · Cited by 372 · see citing works
Beneficial health effects of exercise – the role of IL-6 as a myokine
Pedersen, B. K., & Fischer, C. P. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.02.002 · Cited by 371 · see citing works
The role of IL-6 in mediating the anti-inflammatory effects of exercise.
Petersen, A. M. W., & Pedersen, B. K. (2006) · PubMed · Cited by 354 · 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-citation
Abnormal glucose homeostasis in skeletal muscle–specific PGC-1α knockout mice reveals skeletal muscle–pancreatic β cell crosstalk
Handschin, C., Choi, C. S., Chin, S., Kim, S., Kawamori, D., Kurpad, A. J., Neubauer, N., Hu, J., Mootha, V. K., Kim, Y.-B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31785 · Cited by 335 · see citing works
Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases
Sallam, N., & Laher, I. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7239639 · Cited by 334 · see citing works
Obesity-Induced TNFα and IL-6 Signaling: The Missing Link between Obesity and Inflammation—Driven Liver and Colorectal Cancers
Kern, L., Mittenbühler, M., Vesting, A., Ostermann, A., Wunderlich, C., & Wunderlich, F. (2018) · Cancers · doi:10.3390/cancers11010024 · Cited by 331 · see citing works
The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review
Docherty, S., Harley, R., McAuley, J. J., Crowe, L. A. N., Pedret, C., Kirwan, P., Siebert, S., & Millar, N. L. (2022) · BMC Sports Science Medicine and Rehabilitation · doi:10.1186/s13102-022-00397-2 · Cited by 316 · see citing works
FGF21 as Modulator of Metabolism in Health and Disease
Tezze, C., Romanello, V., & Sandri, M. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00419 · Cited by 313 · see citing works
Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR (Part II)
Vanhees, L., Geladas, N. D., Hansen, D., Kouidi, E. J., Niebauer, J., Reiner, Ž., Cornelissen, V., Adamopoulos, S., Prescott, E., & Börjesson, M. (2011) · European Journal of Preventive Cardiology · doi:10.1177/1741826711430926 · Cited by 309 · see citing works
C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction
Guescini, M., Guidolin, D., Vallorani, L., Casadei, L., Gioacchini, A. M., Tibollo, P., Battistelli, M., Falcieri, E., Battistin, L., Agnati, L. F., et al. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.04.006 · Cited by 294 · see citing works
The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor?
Pedersen, B. K., Steensberg, A., Fischer, C. P., Keller, C., Keller, P., Plomgaard, P., Petersen, E. W., & Febbraio, M. A. (2004) · Proceedings of The Nutrition Society · doi:10.1079/pns2004338 · Cited by 273 · see citing works
Sarcopenia, osteoporosis and frailty
Gielen, E., Dupont, J., Dejaeger, M., & Laurent, M. R. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155638 · Cited by 274 · see citing works
Interleukin-6 regulates pancreatic α-cell mass expansion
Ellingsgaard, H., Ehses, J. A., Hammar, E. B., Van Lommel, L., Quintens, R., Martens, G., Kerr-Conte, J., Pattou, F., Berney, T., Pipeleers, D., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801059105 · Cited by 269 · see citing works
Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition
Nielsen, A. R., Mounier, R., Plomgaard, P., Mortensen, O. H., Penkowa, M., Speerschneider, T., Pilegaard, H., & Pedersen, B. K. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.139618 · Cited by 266 · see citing works
The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling and atrophy
Murton, A. J., Constantin, D., & Greenhaff, P. L. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.10.011 · Cited by 265 · see citing works
Sarcopenia is independently associated with cardiovascular disease in older Korean adults: the Korea National health and nutrition examination survey (KNHANES) from (2009)
Chin, S. O., Rhee, S. Y., Chon, S., Hwang, Y.-C., Jeong, I.-K., Oh, S., Ahn, K. J., Chung, H. Y., Woo, J.-T., Kim, S.-W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060119 · Cited by 252 · see citing works
Contractile C2C12myotube model for studying exercise-inducible responses in skeletal muscle
Nedachi, T., Fujita, H., & Kanzaki, M. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90280.2008 · Cited by 247 · see citing works
The role of exercise-induced myokines in regulating metabolism
Huh, J. Y. (2018) · Archives of Pharmacal Research · doi:10.1007/s12272-017-0994-y · Cited by 242 · see citing works
The Structure of Irisin Reveals a Novel Intersubunit β-Sheet Fibronectin Type III (FNIII) Dimer
Schumacher, M. A., Chinnam, N. B., Ohashi, T., Shah, R., & Erickson, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.516641 · Cited by 240 · see citing works
The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15
Nielsen, A. R., & Pedersen, B. K. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-054 · Cited by 239 · see citing works
Muscle-derived interleukin-6—a possible link between skeletal muscle, adipose tissue, liver, and brain
Pedersen, B. K., & Febbraio, M. (2005) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.04.008 · Cited by 233 · see citing works
Fibroblast growth factor 21 controls mitophagy and muscle mass
Oost, L. J., Kustermann, M., Armani, A., Blaauw, B., & Romanello, V. (2019) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12409 · Cited by 231 · see citing works
Muscle releases alpha-sarcoglycan positive extracellular vesicles carrying miRNAs in the bloodstream
Guescini, M., Canonico, B., Lucertini, F., Maggio, S., Annibalini, G., Barbieri, E., Luchetti, F., Papa, S., & Stocchi, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125094 · Cited by 228 · see citing works
“[2] demonstrated that the cytokine IL-6 is produced and released by muscle fibers in response to acute aerobic exercise.”
Background
Physiological roles of muscle-derived interleukin-6 in response to exercise
Pedersen, B. K., & Fischer, C. P. (2007) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e3280ebb5b3 · Cited by 227 · see citing works
The role of interleukin‐6 in insulin resistance, body fat distribution and energy balance
Hoene, M., & Weigert, C. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2007.00410.x · Cited by 218 · see citing works
Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise
Safdar, A., & Tarnopolsky, M. A. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029827 · Cited by 203 · see citing works
Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing
Baumert, P., Lake, M., Stewart, C. E., Drust, B., & Erskine, R. M. (2016) · European Journal of Applied Physiology · doi:10.1007/s00421-016-3411-1 · Cited by 194 · see citing works
Extracellular Vesicles and Exosomes: Insights From Exercise Science
Nederveen, J. P., Warnier, G., Carlo, A. D., Nilsson, M. I., & Tarnopolsky, M. A. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.604274 · Cited by 192 · see citing works
Evidence for Anti-Inflammatory Effects of Exercise in CKD
Viana, J. L., Kosmadakis, G., Watson, E. L., Bevington, A., Feehally, J., BISHOP, N. C., & Smith, A. C. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013070702 · Cited by 190 · see citing works
An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus
Dekker, M. J., Lee, S., HUDSON, R. W., Kilpatrick, K., Graham, T. E., Ross, R., & Robinson, L. E. (2007) · Metabolism · doi:10.1016/j.metabol.2006.10.015 · Cited by 176 · see citing works
Inflammatory biomarkers in blood of patients with acute brain ischemia
Sotgiu, S., Zanda, B., Marchetti, B., Fois, M. L., Arru, G., Pes, G. M., Salaris, F., Arru, A., Pirisi, A., & Rosati, G. (2006) · European Journal of Neurology · doi:10.1111/j.1468-1331.2006.01280.x · Cited by 174 · see citing works
Regulation of energy balance by inflammation: Common theme in physiology and pathology
Wang, H., & Ye, J. (2014) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-014-9306-8 · Cited by 173 · see citing works
Obesity, adipokines and neuroinflammation
Aguilar‐Valles, A., Inoue, W., Rummel, C. D., & Luheshi, G. N. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.12.023 · Cited by 166 · see citing works
Inflammation, physical activity, and chronic disease: An evolutionary perspective
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Authors: Pedersen
Venue: Journal of Muscle Research and Cell Motility
Publisher: Springer Science and Business Media LLC
Published: 2003
Volume: 24
Issue: 2/3
Pages: 113-119
ISSN: 0142-4319 (ISSN-L)
DOI: 10.1023/a:1026070911202
OpenAlex: W1566764955
Cited by: 564
References: 91
Citations by year: 2026: 19 · 2025: 33 · 2024: 38 · 2023: 52 · 2022: 38 · 2021: 26 · 2020: 31 · 2019: 28 · 2018: 28 · 2017: 32 · 2016: 21 · 2015: 24 · 2014: 23 · 2013: 24 · 2012: 15
FWCI: 11.53
Type: journal article
Language: en
Open access: closed
Locations: Journal of Muscle Research and Cell Motility (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
RMIT Research Repository (RMIT University Library) (submittedVersion)
Figshare (submittedVersion)
Topics: Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: interleukin-6, myokines, physical activity, skeletal muscle, muscle contraction, IL-6 expression, glycogen, energy sensing, adipose tissue, lipolysis, lipid oxidation, TNF-α, insulin resistance, atherosclerosis, cytokines
MeSH terms: Adipose Tissue, Energy Metabolism, Glucose, Humans, Tumor Necrosis Factor-alpha, Exercise, Interleukin-6, Muscle, Skeletal, Muscle Cells, Lipid Metabolism

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Searching for the exercise factor: is IL-6 a candidate?

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