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

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