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 (30 degrees C to 40 degrees C 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-1 beta, TNF-alpha, IFN-gamma, 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 jive stages ranged 1.0% to 2.5%. Pre- and post-stage plasma osmolality in UER ranged277 to 282mOsmol/kg and 23610 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-1 beta (95% at Stage 5), TNF-alpha (168% at Stage 5), IFN-gamma (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-1 beta, 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 I), IL-1 beta (64% at Stage 1). TNF-alpha (101% at Stage 1), IFN-gamma (39% at Stage 1), IL-10 (1100% at Stage I), and IL-1ra (207% at Stage I) concentrations in UER. Multi-stage ultra-marathon competition in the heat resulted in a modest circulatory endotoxaemia accompanied by a pronounced pro-inflammatory cytokiniaemia by post-Stage I. 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 caffein scenario.