Mild endotoxemia, NF-κB translocation, and cytokine increase during exertional heat stress in trained and untrained individuals

Selkirk, G. A.; McLellan, T. M.; Wright, H. E.; Rhind, S. G.

doi:10.1152/ajpregu.00917.2007

Cited by 170Thermoregulation and physiological responsesExercise and Physiological ResponsesCardiovascular and exercise physiology

Mild endotoxemia, NF-κB translocation, and cytokine increase during exertional heat stress in trained and untrained individuals

Selkirk, G. A., McLellan, T. M., Wright, H. E., Rhind, S. G.·2008·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

DOI 10.1152/ajpregu.00917.2007

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Abstract

This study examined endotoxin-mediated cytokinemia during exertional heat stress (EHS). Subjects were divided into trained [TR; n=12, peak aerobic power (VO2peak)=70+/-2 ml.kg lean body mass(-1).min(-1)] and untrained (UT; n=11, VO2peak=50+/-1 ml.kg lean body mass(-1).min(-1)) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber (40 degrees C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5 degrees C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0 degrees C/Exh) were analyzed for endotoxin, lipopolysaccharide binding protein, circulating cytokines, and intranuclear NF-kappaB translocation. Baseline and Exh samples were also stimulated with LPS (100 ng/ml) and cultured in vitro in a 37 degrees C water bath for 30 min. Phenotypic determination of natural killer cell frequency was also determined. Enhanced blood (104+/-6 vs. 84+/-3 ml/kg) and plasma volumes (64+/-4 vs. 51+/-2 ml/kg) were observed in TR compared with UT subjects. EHS produced an increased concentration of circulating endotoxin in both TR (8+/-2 pg/ml) and UT subjects (15+/-3 pg/ml) (range: not detected to 32 pg/ml), corresponding with NF-kappaB translocation and cytokine increases in both groups. In addition, circulating levels of tumor necrosis factor-alpha and IL-6 were also elevated combined with concomitant increases in IL-1 receptor antagonist in both groups and IL-10 in TR subjects only. Findings suggest that the threshold for endotoxin leakage and inflammatory activation during EHS occurs at a lower temperature in UT compared with TR subjects and support the endotoxin translocation hypothesis of exertional heat stroke, linking endotoxin tolerance and heat tolerance.

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Pre-race endotoxin levels in LAB4ANTI were comparable to resting values observed in trained athletes elsewhere (~3.8 ± 2.0 pg/mL).
“These levels are comparable to resting values observed in trained athletes elsewhere at ~3.8 ± 2.0 pg·mL−1 [13], and could have important implications for those individuals with previously raised endotoxin levels (e.g., >20 pg·mL−1) or who are more susceptible to training related GI symptoms.”
From An Exploratory Investigation of Endotoxin Levels in Novice Long Distance Triathletes, and the Effects of a Multi-Strain Probiotic/Prebiotic, Antioxidant Intervention (2016) · cites this paper as [13]

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Authors: Selkirk, G. A., McLellan, T. M., Wright, H. E., & Rhind, S. G.
Affiliations: Defence Research and Development Canada (CA)
York University (CA)
Corresponding author: McLellan, T. M.
ORCID: Wright, H. E.
Rhind, S. G.
Venue: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher: American Physiological Society
Published: 2008-08
Volume: 295
Issue: 2
Pages: R611-R623
ISSN: 0363-6119 (ISSN-L)
1522-1490
DOI: 10.1152/ajpregu.00917.2007
OpenAlex: W1983803767
Cited by: 170
References: 94
Citations by year: 2026: 8 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 13 · 2020: 14 · 2019: 4 · 2018: 9 · 2017: 10 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 15 · 2012: 10
FWCI: 3.62
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
PubMed (publishedVersion)
NPARC (submittedVersion)
Topics: Health Sciences › Medicine › Physiology › Thermoregulation and physiological responses
Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords: exertional heat stress, endotoxemia, lipopolysaccharide-binding protein, NF-κB nuclear translocation, cytokines, TNF-α, interleukin-6, interleukin-1 receptor antagonist, IL-10, trained vs untrained subjects, heat tolerance, endotoxin tolerance, heatstroke, natural killer cells, plasma volume, rectal temperature
MeSH terms: Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Adolescent, Adult, Blood Volume, Body Temperature Regulation, Carrier Proteins, Endotoxins, Physical Exertion, Humans, Inflammation, Killer Cells, Natural, Leukocyte Count, Male, Membrane Glycoproteins, Plasma Volume, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, NF-kappa B, Interleukin-10, Heat Stress Disorders, Bacterial Translocation, Endotoxemia, Active Transport, Cell Nucleus, Interleukin 1 Receptor Antagonist Protein

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Mild endotoxemia, NF-κB translocation, and cytokine increase during exertional heat stress in trained and untrained individuals

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