Circulatory endotoxin concentration and cytokine profile in response to exertional-heat stress during a multi-stage ultra-marathon competition

Exerc Immunol Rev. 2015;21:114-28.


Exertional-heat stress has the potential to disturb intestinal integrity, leading to enhanced permeability of enteric pathogenic micro-organisms and associated clinical manifestations. The study aimed to determine the circulatory endotoxin concentration and cytokine profile of ultra-endurance runners (UER, n=19) and a control group (CON, n=12) during a five stage 230km ultra-marathon (mean ± SD: 27h38min ± 3h55min) conducted in hot and dry environmental conditions (30ºC to 40ºC and 31% to 40% relative humidity). Body mass and tympanic temperature were measured, and venous blood samples were taken before (pre-stage) and immediately after (post-stage) each stage of the ultra-marathon for the analysis of gram-negative bacterial endotoxin, C-reactive protein, cytokine profile (IL-6, IL-1β, TNF-α, IFN-γ, IL-10, and IL- 1ra), and plasma osmolality. Gastrointestinal symptoms and perceptive thermal tolerance rating were also monitored throughout competition. Mean exercise-induced body mass loss over the five stages ranged 1.0% to 2.5%. Pre- and poststage plasma osmolality in UER ranged277 to 282mOsmol/kg and 286 to 297 mOsmol/kg, respectively. Pre-stage concentrations of endotoxin (peak: 21% at Stage 5), C-reactive protein (889% at Stage 3), IL-6 (152% at Stage 2), IL-1β (95% at Stage 5), TNF-α (168% at Stage 5), IFN-γ (102% at Stage 5),IL-10 (1271% at Stage 3), and IL-1ra (106% at Stage 5) increased as the ultra-marathon progressed in UER; while no changes in CON were observed (except for IL-1β, 71% at Stage 5). Pre- to post-stage increases were observed for endotoxin (peak: 22% at Stage 3), C-reactive protein (25% at Stage 1), IL-6 (238% at Stage 1), IL-1β (64% at Stage 1), TNF-α (101% at Stage 1), IFN-γ (39% at Stage 1), IL-10 (1100% at Stage 1), and IL-1ra(207% at Stage 1) concentrations in UER. Multi-stage ultra-marathon competition in the heat resulted in a modest circulatory endotoxaemia accompanied by a pronounced pro-inflammatory cytokinaemia by post-Stage 1, both of which were sustained throughout competition at rest (pre-stage) and after stage completion. Compensatory anti-inflammatory responses and other external factors (i.e., training status, cooling strategies, heat acclimatization, nutrition and hydration) may have contributed towards limiting the extent of pro-inflammatory responses in the current scenario.

Keywords: endurance; gastrointestinal.; heat; inflammation; running.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Athletes
  • Bacterial Translocation
  • C-Reactive Protein / analysis
  • Cytokines / blood*
  • Drinking
  • Electrolytes / administration & dosage
  • Endotoxemia / blood
  • Endotoxemia / etiology*
  • Energy Intake
  • Female
  • Gram-Negative Bacteria / chemistry
  • Heat Exhaustion / blood
  • Heat Exhaustion / etiology
  • Hot Temperature / adverse effects*
  • Humans
  • Inflammation / blood
  • Inflammation / etiology*
  • Inflammation / prevention & control
  • Lipopolysaccharides / blood*
  • Male
  • Osmolar Concentration
  • Physical Exertion / physiology*
  • Running / physiology*
  • Stress, Physiological / immunology
  • Stress, Physiological / physiology*
  • Weight Loss


  • Cytokines
  • Electrolytes
  • Lipopolysaccharides
  • C-Reactive Protein