Gastrointestinal barrier dysfunction, endotoxin neutralizing capacity and immuno-inflammatory mediators following repeated exertional heat stress exposure

Recent evidence in humans has shown a greater endotoxin leakage in sedentary untrained (UT) compared with endurance trained (TR) males at core temperatures below those normally assumed to be essential for the progression of heat illness or heat stroke during acute exertional heat stress (EHS) exposure [1]. Minimal data exists examining the role of gastrointestinal (GI) barrier function, circulating immuno-inflammatory mediators and physiological heat tolerance that accompanies repeated EHS exposures and whether the same cytoprotective responses observed in TR individuals [2] may be induced during repeated EHS in UT. The purpose of this work was to examine the immuno-inflammatory cascades accompanying classical physiological adaptations in untrained males following repeated EHS exposures. Nine UT males (Age = 27 ± 2 years, VO₂peak= 52 ± 2 mL·kgLBM⁻¹·min⁻¹, 17 ± 2% body fatness) walked to exhaustion (EXH) at 4.5 km·h⁻¹ with 2% elevation in a climatic chamber (40°C, 30% R.H.) while wearing encapsulating protective clothing on 9 separate days. Venous whole blood samples were collected at baseline (PRE), 38.0C, 38.5C, 39.0C and EXH on Days 1 and 9, while PRE/EXH samples were drawn on Days 5 and 6. Samples were analyzed for endogenous endotoxin, endotoxin neutralizing capacity (ENC) and for circulating immuno-inflammatory mediators macrophage inflammatory protein (MIP)-1β, IL-6, IL-10, lipopolysaccharide binding protein (LBP), soluble (s) CD14 and extracellular (e) HSP72 by ELISA. In addition, intracellular (i) HSP72 was examined in circulating leukocyte subsets by flow cytometry. Classical physiological adaptations, including reduced HR and increased tolerance time, delta core temperature tolerated, plasma volume and sweat rates were observed during repeated EHS exposure. Mild endotoxemia (21.3 ± 5 pg/mL) was observed at EXH on Days 1, 5, 6, 9 as well as a 14% reduction in ENC (12014 ± 717 vs. 10292 ± 929 ENU/mL) from PRE to EXH on Day 1. Accompanying the changes in endogenous endotoxin and thermoregulatory adaptations were enhanced circulating levels of IL-6, IL-10, LBP, sCD14 as well as cytoprotective increases in both eHSP72 and iHSP72. These findings suggest that GI barrier dysfunction may be an important mechanism of immuno-inflammatory modulation and cytoprotective adaptations observed following repeated EHS exposures.
Exercise and Immunity in Athletic Performance and a Healthy Life, 10th ISEI Symposium (International Society of Exercise and Immunology), July 11-13, 2011, Oxford, UK