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

Abstract

This study examined endotoxin-mediated cytokinemia during exertional heat stress (EHS). Subjects were divided into trained [TR; n = 12, peak aerobic power (V̇o2peak) = 70 ± 2 ml·kg lean body mass−1·min−1] and untrained (UT; n = 11, V̇o2peak= 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°C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5°C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0°C/Exh) were analyzed for endotoxin, lipopolysaccharide binding protein, circulating cytokines, and intranuclear NF-κB translocation. Baseline and Exh samples were also stimulated with LPS (100 ng/ml) and cultured in vitro in a 37°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-κB translocation and cytokine increases in both groups. In addition, circulating levels of tumor necrosis factor-α 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.