Exercise and IL‐6 infusion inhibit endotoxin‐induced TNF‐α production in humans
Abstract
During "nondamaging" exercise, skeletal muscle markedly releases interleukin (IL)-6, and it has been suggested that one biological role of this phenomenon is to inhibit the production of tumor necrosis factor (TNF)- alpha, which is known to cause pathogenesis such as insulin resistance and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli lipopolysaccharide endotoxin (0.06 ng/kg) i.v. to induce low-grade inflammation. In CON, plasma TNF-alpha increased significantly in response to endotoxin. In contrast, during EX, which resulted in elevated IL-6, and rhIL-6, the endotoxin-induced increase in TNF-alpha was totally attenuated. In conclusion, physical exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced by and released from exercising muscles.
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In humans, infusion of rhIL-6, mimicking exercise-induced IL-6 increase, inhibited the increase in endotoxin-induced TNF-α plasma levels.
“In humans, infusion of rhIL-6, an experimental procedure that mimics the increase in IL-6 levels induced by exercise, was able to inhibit the increase in endotoxin-induced TNF-α plasma levels (Starkie 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 Starkie et al., 2003
Exercise prior to endotoxin totally blunted the increase in circulating levels of TNF-α that was observed during a resting situation.
“Exercise prior to endotoxin totally blunted the increase in circulating levels of TNF‐α that was observed during a resting situation.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [113]
Infusion of rhIL-6 prior to endotoxin administration blunts the TNF-α response in humans.
“It was therefore expected that an infusion of rhIL-6 prior to endotoxin administration would also blunt the TNF‐α response in humans and this was in fact what was found (113).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [113]
Healthy subjects were randomized to either rest or exercise prior to endotoxin administration.
“We infused a very low dose of Escherichia coli endotoxin to healthy subjects, who were randomized to either rest or exercise prior to the endotoxin administration (113).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [113]
In healthy humans, a single exercise bout or an IL-6 infusion reduced the TNF increase caused by lipopolysaccharide infusion.
“In healthy humans, one bout of exercise or an IL-6 infusion blunted the increase in circulating levels of TNF induced by infusion of lipopolysaccharide128.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [128]
Increasing IL-6, either by exercise or by infusion, blunts the inflammatory effect of TNF.
“An important paper demonstrating that increasing IL-6 either by exercise or by infusion blunts the inflammatory effect of TNF.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [128]
rhIL-6 infusion inhibits the endotoxin-induced increase in circulating levels of TNF-α in healthy humans.
“In addition, rhIL-6 infusion inhibits the endotoxin-induced increase in circulating levels of TNF-α in healthy humans [69].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [69]
The effect of exercise on the endotoxin-induced TNF-α response could be mimicked by infusion of IL-6, suggesting that IL-6 may be involved in mediating the anti-inflammatory effects of exercise.
“Moreover, the effect of exercise could be mimicked by infusion of IL-6, suggesting that IL-6 may be involved in mediating the anti-inflammatory effects of exercise [69].”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [69]
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“demonstrated that exercise and IL-6 infusion inhibit TNF-α production, suggesting that IL-6 might mediate anti-inflammatory activity during exercise [74].”
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- Authors
- Starkie, R., Ostrowski, S. R., Jauffred, S., Febbraio, M., & Pedersen, B. K.
- Affiliations
- University of Copenhagen (DK)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2003-03-05
- Volume
- 17
- Issue
- 8
- Pages
- 1-10
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2033124959
- Cited by
- 790
- References
- 23
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 24 · 2023: 33 · 2022: 51 · 2021: 60 · 2020: 44 · 2019: 33 · 2018: 48 · 2017: 34 · 2016: 36 · 2015: 39 · 2014: 44 · 2013: 53 · 2012: 38
- FWCI
- 21.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion)
- Funders
- Danmarks Grundforskningsfond (504-14)
- Novo Nordisk Fonden
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- interleukin-6, TNF-α, endotoxin, lipopolysaccharide, physical activity, anti-inflammatory activity, skeletal muscle, low-grade inflammation, insulin resistance, atherosclerosis
- MeSH terms
- Analysis of Variance, Humans, Infusions, Intravenous, Lipopolysaccharides, Male, Posture, Recombinant Proteins, Tumor Necrosis Factor-alpha, Exercise, Interleukin-6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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