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Cited by 1,095Exercise and Physiological ResponsesCardiovascular and exercise physiologyMuscle metabolism and nutrition

Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6

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Steensberg, Adam, van Hall, Gerrit, Osada, Takuya, Sacchetti, Massimo, Saltin, Bengt, Pedersen, Bente Klarlund·2000·The Journal of Physiology
DOI 10.1111/j.1469-7793.2000.00237.xPMC PMC2270169
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Abstract

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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  • 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.

    “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]

    The paper’s study summary reports a 19-fold rise in arterial plasma IL-6 after 5 hours of exercise, supporting that part of the claim. However, Methods describes one-legged knee-extensor exercise at 40% of peak power output, not 40% VO2 max; its subjects were physically active men aged 22–33. The paper does not report a 30-minute walk in sedentary middle-aged men. Page numbers were not available in our copy. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • IL-6 is an exercise factor and skeletal muscle is a secretory organ with endocrine functions.

    “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]

  • Skeletal muscle works as an endocrine organ that can produce and secrete hundreds of myokines exerting autocrine, paracrine, or endocrine effects.

    “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]

  • Skeletal muscle produces and releases interleukin-6 (IL-6) into the circulation.

    “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]

  • IL-6 has been the most extensively studied myokine since its discovery in 2000.

    “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]

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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
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2000-11
Volume
529
Issue
1
Pages
237-242
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1111/j.1469-7793.2000.00237.x
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
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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 › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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