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

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 post-stage 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 (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.