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Cited by 293Exercise and Physiological ResponsesAntioxidant Activity and Oxidative StressMuscle metabolism and nutrition

Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle

Fischer, Christian P., Hiscock, Natalie J., Penkowa, Milena, Basu, Samar, Vessby, Bengt, Kallner, Anders, Sjöberg, Lars‐Börje, Pedersen, Bente K.·2004·The Journal of Physiology
DOI 10.1113/jphysiol.2004.066779
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Abstract

Contracting human skeletal muscle is a major contributor to the exercise-induced increase of plasma interleukin-6 (IL-6). Although antioxidants have been shown to attenuate the exercise-induced increase of plasma IL-6, it is unknown whether antioxidants inhibit transcription, translation or translocation of IL-6 within contracting human skeletal muscle. Using a single-blind placebo-controlled design with randomization, young healthy men received an oral supplementation with either a combination of ascorbic acid (500 mg day(-1)) and RRR-alpha-tocopherol (400 i.u. day(-1)) (Treatment, n= 7), or placebo (Control, n= 7). After 28 days of supplementation, the subjects performed 3 h of dynamic two-legged knee-extensor exercise at 50% of their individual maximal power output. Muscle biopsies from vastus lateralis were obtained at rest (0 h), immediately post exercise (3 h) and after 3 h of recovery (6 h). Leg blood flow was measured using Doppler ultrasonography. Plasma IL-6 concentration was measured in blood sampled from the femoral artery and vein. The net release of IL-6 was calculated using Fick's principle. Plasma vitamin C and E concentrations were elevated in Treatment compared to Control. Plasma 8-iso-prostaglandin F(2alpha), a marker of lipid peroxidation, increased in response to exercise in Control, but not in Treatment. In both Control and Treatment, skeletal muscle IL-6 mRNA and protein levels increased between 0 and 3 h. In contrast, the net release of IL-6 from the leg, which increased during exercise with a peak at 3.5 h in Control, was completely blunted during exercise in Treatment. The arterial plasma IL-6 concentration from 3 to 4 h, when the arterial IL-6 levels peaked in both groups, was approximately 50% lower in the Treatment group compared to Control (Treatment versus Control: 7.9 pg ml(-1), 95% confidence interval (CI) 6.0-10.7 pg ml(-1), versus 19.7 pg ml(-1), CI 13.8-29.4 pg ml(-1), at 3.5 h, P < 0.05 between groups). Moreover, plasma interleukin-1 receptor antagonist (IL-1ra), C-reactive protein and cortisol levels all increased after the exercise in Control, but not in Treatment. In conclusion, our results show that supplementation with vitamins C and E attenuated the systemic IL-6 response to exercise primarily via inhibition of the IL-6 protein release from the contracting skeletal muscle per se.

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  • Antioxidant supplementation totally inhibited the release of IL-6 from exercising human muscle as well as the exercise-induced increase in systemic levels of cortisol.

    “Moreover, antioxidant supplementation totally inhibited the release of IL-6 from exercising human muscle as well as the exercise-induced increase in systemic levels of cortisol (206).”

    From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [206]

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Authors
Fischer, C. P., Hiscock, N. J., Penkowa, M., Basu, S., Vessby, B., Kallner, A., Sjöberg, L., & Pedersen, B. K.
Affiliations
  • Copenhagen University Hospital (DK)
  • Copenhagen Muscle Research Centre (DK)
  • University of Copenhagen (DK)
  • Uppsala University (SE)
  • Karolinska University Hospital (SE)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2004-07
Volume
558
Issue
2
Pages
633-645
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2004.066779
OpenAlex
W1812661065
Cited by
293
References
48
Citations by year
2026: 8 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 24 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 10 · 2016: 15 · 2015: 17 · 2014: 17 · 2013: 22 · 2012: 17
FWCI
15.59
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 8 d)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Velux Stiftung
  • Augustinus Fonden
Topics
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
interleukin-6, vitamin C, vitamin E, antioxidants, skeletal muscle contraction, alpha-tocopherol, lipid peroxidation, 8-isoprostane, vastus lateralis, knee extension exercise, interleukin-1 receptor antagonist, C-reactive protein, cortisol, muscle blood flow
MeSH terms
Adult, Antioxidants, Ascorbic Acid, Blood Glucose, C-Reactive Protein, Humans, Hydrocortisone, Male, Muscle Contraction, Sialoglycoproteins, Vitamin E, Lipid Peroxidation, Exercise, Interleukin-6, Gene Expression, Muscle, Skeletal, Interleukin 1 Receptor Antagonist Protein

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