Mild endotoxemia, NF-[kappa]B 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.sub.2peak]) = 70 [+ or -] 2 ml*kg lean body [mass.sup.-1]*[min.sup.-1]] and untrained (UT; n = 11, [Vo.sub.2peak] = 50 [+ or -] 1 ml*kg lean body [mass.sup.-1*[min.sup.-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 cytoldnes, 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 [+ or -] 6 vs. 84 [+ or -] 3 ml/kg) and plasma volumes (64 [+ or -] 4 vs. 51 [+ or -] 2 ml/kg) were observed in TR compared with UT subjects. EHS produced an increased concentration of circulating endotoxin in both TR (8 [+ or -] 2 pg/ml) and UT subjects (15 [+ or -] 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 U T compared with TR subjects and support the endotoxin translocation hypothesis of exertional heat stroke, linking endotoxin tolerance and heat tolerance. splanchnic permeability; immune function; blood volume; cardiovascular/thermoregulatory strain; flow cytometry