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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 295; no. 2; p. R611
• Main Authors: Selkirk, G A, McLellan, T M, Wright, H E, Rhind, S G
• Format: Journal Article
• Language: English
• Published: United States 01.08.2008
• Subjects: Active Transport, Cell Nucleus; Acute-Phase Proteins; Adolescent; Adult; Bacterial Translocation; Blood Volume; Body Temperature Regulation; Carrier Proteins - blood; Cytokines - blood; Endotoxemia - blood; Endotoxemia - immunology; Endotoxemia - physiopathology; Endotoxins - blood; Heat Stress Disorders - blood; Heat Stress Disorders - immunology; Heat Stress Disorders - physiopathology; Humans; Inflammation - blood; Inflammation - immunology; Inflammation - physiopathology; Interleukin 1 Receptor Antagonist Protein - blood; Interleukin-10 - blood; Interleukin-6 - blood; Killer Cells, Natural - immunology; Leukocyte Count; Male; Membrane Glycoproteins - blood; NF-kappa B - blood; Physical Exertion; Plasma Volume; Tumor Necrosis Factor-alpha - blood
• ISSN: 0363-6119
• DOI: 10.1152/ajpregu.00917.2007

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.