Mild endotoxemia, NF-{kappa}B translocation, and cytokine increase during exertional heat stress in trained and untrained individuals

1 Defence Research and Development Canada-Toronto, Toronto; and 2 Kinesiology and Health Science Graduate Programme, York University, Toronto, Ontario, Canada Submitted 21 December 2007 ; accepted in final form 17 June 2008 This study examined endotoxin-mediated cytokinemia during exertional heat stress (EHS). Subjects were divided into trained [TR; n = 12, peak aerobic power ( O 2peak ) = 70 ± 2 ml·kg lean body mass –1 ·min –1 ] and untrained (UT; n = 11, O 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°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- B 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- B translocation and cytokine increases in both groups. In addition, circulating levels of tumor necrosis factor- 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. splanchnic permeability; immune function; blood volume; cardiovascular/thermoregulatory strain; flow cytometry Address for reprint requests and other correspondence: T. M. McLellan, Defence R & D Canada-Toronto, 1133 Sheppard Ave. E., Toronto, ON, Canada M3M 3B9 (e-mail: tom.mclellan{at}drdc-rddc.gc.ca )