Pro‐ and anti‐inflammatory cytokine balance in strenuous exercise in humans
Open accessAbstract
1. The present study investigates to what extent and by which time course prolonged strenuous exercise influences the plasma concentration of pro-inflammatory and inflammation responsive cytokines as well as cytokine inhibitors and anti-inflammatory cytokines. 2. Ten male subjects (median age 27.5 years, range 24-37) completed the Copenhagen Marathon 1997 (median running time 3 : 26 (h : min), range 2 : 40-4 : 20). Blood samples were obtained before, immediately after and then every 30 min in a 4 h post-exercise recovery period. 3. The plasma concentrations of tumour necrosis factor (TNF)alpha, interleukin (IL)-1beta, IL-6, IL-1ra, sTNF-r1, sTNF-r2 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The highest concentration of IL-6 was found immediately after the race, whereas IL-1ra peaked 1 h post exercise (128-fold and 39-fold increase, respectively, as compared with the pre-exercise values). The plasma level of IL-1beta, TNFalpha, sTNF-r1 and sTNF-r2 peaked in the first hour after the exercise (2. 1-, 2.3-, 2.7- and 1.6-fold, respectively). The plasma level of IL-10 showed a 27-fold increase immediately post exercise. 4. In conclusion, strenuous exercise induces an increase in the pro-inflammatory cytokines TNFalpha and IL-1beta and a dramatic increase in the inflammation responsive cytokine IL-6. This is balanced by the release of cytokine inhibitors (IL-1ra, sTNF-r1 and sTNF-r2) and the anti-inflammatory cytokine IL-10. The study suggests that cytokine inhibitors and anti-inflammatory cytokines restrict the magnitude and duration of the inflammatory response to exercise.
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After a marathon, plasma IL-6, IL-1RA, IL-10 and TNF are higher than baseline immediately after exercise, peak 1-2 hours after exercise and remain elevated for about 4 hours.
“plasma levels of several cytokines (IL-6, IL-1RA, IL-10 and tumour necrosis factor (TNF)) were higher than baseline levels when collected immediately after exercise, peaking 1–2 h after exercise and remaining elevated for ~4 h after exercise30.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [30]
Acute exercise responses typically focus on maintaining metabolic homeostasis, with acute inflammation balanced by anti-inflammatory mediators and shifts in fuel utilization.
“Typically, acute exercise exposure is associated with responses focused on the maintenance of metabolic homeostasis, with acute inflammation balanced by anti-inflammatory mediators30 and accommodating shifts in fuel utilization.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [30]
Exercise affects immune function by mobilizing and altering cytokines and immune cells such as neutrophils, leukocytes and natural killer cells.
“The broad effects of exercise on immune function implicate mobilization and altered function of cytokines and immune cells, such as neutrophils, leukocytes and natural killer cells (FIG. 3; Supplementary Table 1)30,122,123.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [30]
An acute exercise bout may first be pro-inflammatory, then offset by an anti-inflammatory response.
“As shown in humans, an acute bout of exercise might be initially pro-inflammatory, but subsequently this effect is offset by an anti-inflammatory response30,124.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [30]
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 [65]
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 [65]
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- Authors
- Ostrowski, K., Rohde, T., Asp, S., Schjerling, P., & Pedersen, B. K.
- Affiliations
- Rigshospitalet (DK)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 1999-02
- Volume
- 515
- Issue
- 1
- Pages
- 287-291
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2269132
- OpenAlex
- W2157554312
- Cited by
- 1,014
- References
- 26
- Citations by year
- 2026: 31 · 2025: 25 · 2024: 30 · 2023: 47 · 2022: 50 · 2021: 42 · 2020: 41 · 2019: 46 · 2018: 34 · 2017: 39 · 2016: 50 · 2015: 41 · 2014: 57 · 2013: 64 · 2012: 37
- FWCI
- 19.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Danmarks Grundforskningsfond
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Keywords
- strenuous exercise, cytokines, inflammation, marathon running, TNF-α, IL-1β, interleukin-6, interleukin-1 receptor antagonist, soluble TNF receptors, IL-10, cytokine inhibitors, post-exercise recovery, plasma cytokine concentrations
- MeSH terms
- Adult, Enzyme-Linked Immunosorbent Assay, Humans, Inflammation, Interleukins, Male, Physical Endurance, Plasma Volume, Running, Time Factors, Tumor Necrosis Factor-alpha, Exercise, Cytokines
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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