Mild endotoxemia, NF-kappaB 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 (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 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-kappaB 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-kappaB 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.
Selkirk
G A
GA
Defence R & D Canada-Toronto, 1133 Sheppard Ave. E., Toronto, ON, Canada M3M 3B9.
McLellan
T M
TM
Wright
H E
HE
Rhind
S G
SG
D021581:Active Transport, Cell Nucleus; D000209:Acute-Phase Proteins; D000293:Adolescent; D000328:Adult; D018988:Bacterial Translocation; D001810:Blood Volume; D001833:Body Temperature Regulation; D002352:Carrier Proteins / Q000097:blood; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D004731:Endotoxins / Q000097:blood; D018882:Heat Stress Disorders / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D016328:NF-kappa B / Q000097:blood*; D005082:Physical Exertion; D010953:Plasma Volume; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D004731:Endotoxins; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C508609:IL10 protein, human; C507763:IL1RN protein, human; C508600:IL6 protein, human