The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6
Open accessAbstract
1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL-6 accumulating in the blood. 2. This was studied in six healthy males, who performed one-legged dynamic knee extensor exercise for 5 h at 25 W, which represented 40% of peak power output (Wmax). Arterial-femoral venous (a-fv) differences over the exercising and the resting leg were obtained before and every hour during the exercise. Leg blood flow was measured in parallel by the ultrasound Doppler technique. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). 3. Arterial plasma concentrations for IL-6 increased 19-fold compared to rest. The a-fv difference for IL-6 over the exercising leg followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min-1 (kg active muscle)-1 (range, 3.96-9.69 ng min-1 kg-1). 4. The net IL-6 release from the muscle over the last 2 h of exercise was 17-fold higher than the elevation in arterial IL-6 concentration and at 5 h of exercise the net release during 1 min was half of the IL-6 content in the plasma. This indicates a very high turnover of IL-6 during muscular exercise. We suggest that IL-6 produced by skeletal contracting muscle contributes to the maintenance of glucose homeostasis during prolonged exercise.
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In the citing paper
“Studies have shown that IL-6 release during a 30 min walk at 50% VO2 max in sedentary middle-aged men is minimal, whereas prolonged physical activity, such as 5 h at 40% VO2 max leads to a 19-fold increase in IL-6 levels [42,43,44].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [42]
Experimental — accuracy not yet measuredIn the citing paper
“identified IL-6 as an exercise factor and skeletal muscle as a secretory organ with endocrine functions.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [5]
In the citing paper
“During the past couple of decades, it has been apparent that skeletal muscle works as an endocrine organ, which can produce and secrete hundreds of myokines that exert their effects in either autocrine, paracrine, or endocrine manners.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [5]
In the citing paper
“Our finding in 2000 that skeletal muscle produced and released interleukin-6 (IL-6) into the circulation (5)”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [5]
In the citing paper
“Of the myokines, IL-6 has been the most extensively studied since its discovery in 2000 (REF.16).”
From Exerkines in health, resilience and disease (2022) · cites this paper as [16]
In the citing paper
“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 [64]
In the citing paper
“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 [64]
In the citing paper
“circulating levels rising in proportion to exercise duration, intensity, and the degree of muscle glycogen depletion [ 5 , 6 ]”
From IL-6 Activity is Required for Maximal Catecholamine Release During High-Intensity Exercise in Men (2026) · cites this paper as [5]
In the citing paper
“Interleukin-6 (IL-6) is released from human skeletal muscle during exercise [ 5 ]”
From IL-6 Activity is Required for Maximal Catecholamine Release During High-Intensity Exercise in Men (2026) · cites this paper as [5]
In the citing paper
“during moderate-intensity exercise, IL-6 release occurs more gradually and is driven by IL-6 gene transcription, which is activated in response to declining muscle glycogen levels [ 5 , 6 , 12 ]”
From IL-6 Activity is Required for Maximal Catecholamine Release During High-Intensity Exercise in Men (2026) · cites this paper as [5]
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Citations
Cites
Exercise and the immune system: regulation, integration, and adaptation
Pedersen, B. K., & Hoffman-Goetz, L. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.1055 · Cited by 1,710
Self-citationPro‐ and anti‐inflammatory cytokine balance in strenuous exercise in humans
Ostrowski, K., Rohde, T., Asp, S., Schjerling, P., & Pedersen, B. K. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.287ad.x · Cited by 1,014
Self-citationEvidence that interleukin-6 is produced in human skeletal muscle during prolonged running
Ostrowski, K., Rohde, T., Zacho, M., Asp, S., & Pedersen, B. K. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.949bp.x · Cited by 673
Self-citationSMITH, L. L. (1991) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199105000-00006 · Cited by 471
Exercise‐induced increase in serum interleukin‐6 in humans is related to muscle damage.
Brüünsgaard, H., Galbo, H., Halkjær-Kristensen, J., Johansen, T., MacLean, D. A., & Pedersen, B. K. (1997) · The Journal of Physiology · doi:10.1113/jphysiol.1997.sp021972 · Cited by 455
Self-citationA trauma‐like elevation of plasma cytokines in humans in response to treadmill running
Ostrowski, K., Hermann, C., Bangash, A., Schjerling, P., Nielsen, J. N., & Pedersen, B. K. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.889ba.x · Cited by 398
Self-citationDynamic knee extension as model for study of isolated exercising muscle in humans
Andersen, P., Adams, R. P., Sjøgaard, G., Thorboe, A., & Saltin, B. (1985) · Journal of Applied Physiology · doi:10.1152/jappl.1985.59.5.1647 · Cited by 385
Self-citationDose-Dependent Effects of Recombinant Human Interleukin-6 on Glucose Regulation
Tsigos, C., Papanicolaou, D. A., Kyrou, I., Defensor, R., Mitsiadis, C. S., & Chrousos, G. P. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4422 · Cited by 324 · cited 1×
“Moreover, it has been demonstrated that injection of recombinant human IL-6 (rhIL-6) into humans increases the fasting blood glucose concentration in a dose-dependent manner (Tsigos et al. 1997).”
BackgroundCarbohydrate and the cytokine response to 2.5 h of running
Nehlsen-Cannarella, S. L., Fagoaga, O. R., Nieman, D. C., Henson, D. A., Butterworth, D. E., Schmitt, R. L., Bailey, E. M., Warren, B. J., Utter, A., & Davis, J. M. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.82.5.1662 · Cited by 311
Rådegran, G. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.83.4.1383 · Cited by 296
Cited by
Sorted by citations
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
Self-citationMuscles, 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
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
Self-citationMuscle–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
“Our finding in 2000 that skeletal muscle produced and released interleukin-6 (IL-6) into the circulation (5) as well as research during the subsequent years, demonstrating that IL-6 has multiple metabolic effects in other parts of the body (6), identified IL-6 as an exercise factor and skeletal muscle as a secretory o…”
BackgroundSelf-citationIL-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
Self-citation
Metadata
- Authors
- Steensberg, A., van Hall, G., Osada, T., Sacchetti, M., Saltin, B., & Pedersen, B. K.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Pedersen, Bente Klarlund
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2000-11
- Volume
- 529
- Issue
- 1
- Pages
- 237-242
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2270169
- OpenAlex
- W2130248772
- Cited by
- 1,095
- References
- 31
- Citations by year
- 2026: 64 · 2025: 47 · 2024: 67 · 2023: 63 · 2022: 70 · 2021: 61 · 2020: 45 · 2019: 47 · 2018: 49 · 2017: 36 · 2016: 47 · 2015: 46 · 2014: 46 · 2013: 51 · 2012: 36
- FWCI
- 24.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- interleukin-6, skeletal muscle, physical activity, plasma cytokine concentrations, muscle blood flow, glucose homeostasis, prolonged exercise, knee extension exercise
- MeSH terms
- Adult, Humans, Leg, Male, Muscle Contraction, Regional Blood Flow, Time Factors, Exercise, Interleukin-6, Ergometry, Muscle, Skeletal
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