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Am J Physiol Regul Integr Comp Physiol 295: R611-R623, 2008. First published June 18, 2008; doi:10.1152/ajpregu.00917.2007
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EXERCISE AND RESPIRATORY PHYSIOLOGY

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

G. A. Selkirk,2 T. M. McLellan,1,2 H. E. Wright,2 and S. G. Rhind1,2

1Defence Research and Development Canada-Toronto, Toronto; and 2Kinesiology 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 (VO2peak) = 70 ± 2 ml·kg lean body mass–1·min–1] and untrained (UT; n = 11, VO2peak = 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-{kappa}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-{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.

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)




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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
G. A. Selkirk, T. M. McLellan, H. E. Wright, and S. G. Rhind
Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R575 - R586.
[Abstract] [Full Text] [PDF]




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