Int J Sports Med 2015; 36(03): 262-270
DOI: 10.1055/s-0034-1389904
© Georg Thieme Verlag KG Stuttgart · New York

Systemic LPS and Inflammatory Response during Consecutive Days of Exercise in Heat

M. D. Barberio
1   Children’s National Medical Center, Center for Genetic Medicine Research, Washington, D.C., United States
4   School of Kinesiology, Auburn University, Auburn, AL, United States
D. J. Elmer
2   Department of Kinesiology, Berry College, Mount Berry, GA, United States
4   School of Kinesiology, Auburn University, Auburn, AL, United States
R. H. Laird
1   Children’s National Medical Center, Center for Genetic Medicine Research, Washington, D.C., United States
3   Department of Exercise Science & Physical Education, McDaniel College, Westminster, MD, United Sates
K. A. Lee
4   School of Kinesiology, Auburn University, Auburn, AL, United States
B. Gladden
4   School of Kinesiology, Auburn University, Auburn, AL, United States
D. D. Pascoe
4   School of Kinesiology, Auburn University, Auburn, AL, United States
› Author Affiliations
Further Information

Publication History

accepted after revision 25 July 2014

Publication Date:
19 December 2014 (online)


This investigation studied circulating LPS activity, potential intestinal damage, and the systemic inflammatory response (SIR) during the exercise heat acclimation process. 8 healthy males (Age=24±3 years) ran in a hot environment on 5 consecutive days until core temperature (Tc) was elevated 2°C above rest. Plasma was obtained pre-, post-, 1 h post-, and 3 h post-exercise on the 1st, 3rd, and 5th day of exercise and analyzed for TNF-α, IL-6, IL-10, IL-1ra, LPS, and intestinal fatty acid-binding protein (I-FABP). Plasma LPS (1.1 EU·ml−1±0.1 vs. 0.7 EU·ml−1±0.03; P<0.01) and I-FABP (930.7 pg·ml−1±149.0 vs. 640.2 pg·ml−1±125.0; P<0.001) were significantly increased post-exercise each. The SIR remained largely unchanged during the study except for TNF-α. Plasma TNF-α was significantly lower on Day 5 at 1 h (3.2 pg·ml−1±0.6 vs. 4.5 pg·ml−1±0.8; P=0.01) and 3 h (3.6 pg·ml−1±0.8 vs. 4.8 pg·ml−1±0.9; P=0.05) post-exercise as compared to Day 1. Findings indicate that adaptations to exercise in the heat resulting in reductions of intestinal damage and plasma LPS activity require longer time periods in moderately trained males.

  • References

  • 1 Ashton T, Young IS, Davison GW, Rowlands CC, McEneny J, Van Blerk C, Jones E, Peters JR, Jackson SK. Exercise-induced endotoxemia: the effect of ascorbic acid supplementation. Free Radic Biol Med 2003; 35: 284-291
  • 2 Bosenberg AT, Brock-Utne JG, Gaffin SL, Wells MT, Blake GT. Strenuous exercise causes systemic endotoxemia. J Appl Physiol 1988; 65: 106-108
  • 3 Bouchama A, al-Sedairy S, Siddiqui S, Shail E, Rezeig M. Elevated pyrogenic cytokines in heatstroke. Chest 1993; 104: 1498-1502
  • 4 Bouchama A, Knochel JP. Heat stroke. N Engl J Med 2002; 346: 1978-1988
  • 5 Bouchama A, Ollivier V, Roberts G, Al Mohanna F, de Prost D, Eldali A, Saussereau E, El-Sayed R, Chollet-Martin S. Experimental heatstroke in baboon: analysis of the systemic inflammatory response. Shock 2005; 24: 332-335
  • 6 Bouchama A, Parhar RS, el-Yazigi A, Sheth K, al-Sedairy S. Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke. J Appl Physiol 1991; 70: 2640-2644
  • 7 Bouchama A, Roberts G, Al Mohanna F, El-Sayed R, Lach B, Chollet-Martin S, Ollivier V, Al Baradei R, Loualich A, Nakeeb S, Eldali A, de Prost D. Inflammatory, hemostatic, and clinical changes in a baboon experimental model for heatstroke. J Appl Physiol 2005; 98: 697-705
  • 8 Brock-Utne JG, Gaffin SL, Wells MT, Gathiram P, Sohar E, James MF, Morrell DF, Norman RJ. Endotoxaemia in exhausted runners after a long-distance race. S Afr Med J 1988; 73: 533-536
  • 9 Camus G, Poortmans J, Nys M, Deby-Dupont G, Duchateau J, Deby C, Lamy M. Mild endotoxaemia and the inflammatory response induced by a marathon race. Clin Sci (Lond) 1997; 92: 415-422
  • 10 Chen HI, Hsieh SY, Yang FL, Hsu YH, Lin CC. Exercise training attenuates septic responses in conscious rats. Med Sci Sports Exerc 2007; 39: 435-442
  • 11 Derikx JP, Matthijsen RA, de Bruine AP, van Dam RM, Buurman WA, Dejong CH. A new model to study intestinal ischemia-reperfusion damage in man. J Surg Res 2011; 166: 222-226
  • 12 Derikx JP, Vreugdenhil AC, Van den Neucker AM, Grootjans J, van Bijnen AA, Damoiseaux JG, van Heurn LW, Heineman E, Buurman WA. A pilot study on the noninvasive evaluation of intestinal damage in celiac disease using I-FABP and L-FABP. J Clin Gastroenterol 2009; 43: 727-733
  • 13 Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974; 37: 247-248
  • 14 Dokladny K, Moseley PL, Ma TY. Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability. Am J Physiol 2006; 290: G204-G212
  • 15 Fernandez-Botran R. Soluble cytokine receptors: their role in immunoregulation. FASEB J 1991; 5: 2567-2574
  • 16 Garrett AT, Creasy R, Rehrer NJ, Patterson MJ, Cotter JD. Effectiveness of short-term heat acclimation for highly trained athletes. Eur J Appl Physiol 2012; 5: 1827-1837
  • 17 Hailes WS, Slivka D, Cuddy J, Ruby BC. Human plasma inflammatory response during 5 days of exercise training in the heat. J Therm Biol 2011; 36: 277-282
  • 18 Hall DM, Baumgardner KR, Oberley TD, Gisolfi CV. Splanchnic tissues undergo hypoxic stress during whole body hyperthermia. Am J Physiol 1999; 276: G1195-G1203
  • 19 Hall DM, Buettner GR, Matthes RD, Gisolfi CV. Hyperthermia stimulates nitric oxide formation: electron paramagnetic resonance detection of NO-heme in blood. J Appl Physiol 1994; 77: 548-553
  • 20 Hall DM, Buettner GR, Oberley LW, Xu L, Matthes RD, Gisolfi CV. Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. Am J Physiol 2001; 280: H509-H521
  • 21 Harriss DJ, Atkinson G. Ethical standards in sport and exercise science research: 2014 update. Int J Sports Med 2013; 34: 1025-1028
  • 22 Hosick PA, Berry MP, McMurray RG, Cooper ES, Hackney AC. Relationship between change in core temperature and change in cortisol and TNF alpha during exercise. J Therm Biol 2010; 35: 348-353
  • 23 Jeukendrup AE, Vet-Joop K, Sturk A, Stegen JH, Senden J, Saris WH, Wagenmakers AJ. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. Clin Sci (Lond) 2000; 98: 47-55
  • 24 Kregel KC, Wall PT, Gisolfi CV. Peripheral vascular responses to hyperthermia in the rat. J Appl Physiol 1988; 64: 2582-2588
  • 25 Kuennen MR, Gillum TL, Dokladny K, Bedrick EJ, Schneider SM, Moseley PL. Thermotolerance and heat acclimation may share a common mechanism in humans. Am J Physiol 2011; 301: R524-R533
  • 26 Lambert GP, Gisolfi CV, Berg DJ, Moseley PL, Oberley LW, Kregel KC. Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J Appl Physiol 2002; 92: 1750-1761
  • 27 Leon LR, Helwig BG. Heat stroke: role of the systemic inflammatory response. J Appl Physiol 2010; 109: 1980-1988
  • 28 Lin MT, Liu HH, Yang YL. Involvement of interleukin-1 receptor mechanisms in development of arterial hypotension in rat heatstroke. Am J Physiol 1997; 273: H2072-H2077
  • 29 Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine 2008; 42: 145-151
  • 30 Marshall JC. Lipopolysaccharide: an endotoxin or an exogenous hormone?. Clin Infect Dis 2005; 41 (Suppl. 07) S470-S480
  • 31 Moran DS. Stress evaluation by the physiological strain index (PSI). Journal of basic and clinical physiology and pharmacology. J Basic Clin Physiol Pharmacol 2000; 11: 403-423
  • 32 Nielsen B. Heat acclimation – mechanisms of adaptation to exercise in the heat. Int J Sports Med 1998; 19 (Suppl. 02) S154-S156
  • 33 Nieman DC, Henson DA, Dumke CL, Oley K, McAnulty SR, Davis JM, Murphy EA, Utter AC, Lind RH, McAnulty LS, Morrow JD. Ibuprofen use, endotoxemia, inflammation, and plasma cytokines during ultramarathon competition. Brain Behav Immun 2006; 20: 578-584
  • 34 Novitsky TJ. Limitations of the Limulus amebocyte lysate test in demonstrating circulating lipopolysaccharides. Ann N Y Acad Sci 1998; 851: 416-421
  • 35 Osada T, Katsumura T, Hamaoka T, Inoue S, Esaki K, Sakamoto A, Murase N, Kajiyama J, Shimomitsu T, Iwane H. Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension. J Appl Physiol 1999; 86: 709-719
  • 36 Otte JA, Oostveen E, Geelkerken RH, Groeneveld AB, Kolkman JJ. Exercise induces gastric ischemia in healthy volunteers: a tonometry study. J Appl Physiol 2001; 91: 866-871
  • 37 Pals KL, Chang RT, Ryan AJ, Gisolfi CV. Effect of running intensity on intestinal permeability. J Appl Physiol 1997; 82: 571-576
  • 38 Pandolf KB. Time course of heat acclimation and its decay. Int J Sports Med 1998; 19 (Suppl. 02) S157-S160
  • 39 Peake J, Peiffer JJ, Abbiss CR, Nosaka K, Okutsu M, Laursen PB, Suzuki K. Body temperature and its effect on leukocyte mobilization, cytokines and markers of neutrophil activation during and after exercise. Eur J App Physiol 2008; 102: 391-401
  • 40 Petersen AMW, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol 2005; 98: 1154-1162
  • 41 Rhind SG, Gannon GA, Shephard RJ, Buguet A, Shek PN, Radomski MW. Cytokine induction during exertional hyperthermia is abolished by core temperature clamping: neuroendocrine regulatory mechanisms. Int J Hyperthermia 2004; 20: 503-516
  • 42 Rowell L. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev 1974; 54: 75
  • 43 Rowell LB, Brengelmann GL, Blackmon JR, Twiss RD, Kusumi F. Splanchnic blood flow and metabolism in heat-stressed man. J Appl Physiol 1968; 24: 475-484
  • 44 Rowell LB, Marx HJ, Bruce RA, Conn RD, Kusumi F. Reductions in cardiac output, central blood volume, and stroke volume with thermal stress in normal men during exercise. J Clin Invest 1966; 45: 1801-1816
  • 45 Sakurada S, Hales JR. A role for gastrointestinal endotoxins in enhancement of heat tolerance by physical fitness. J Appl Physiol 1998; 84: 207-214
  • 46 Selkirk GA, McLellan TM, Wright HE, Rhind SG. Mild endotoxemia, NF-kappaB translocation, and cytokine increase during exertional heat stress in trained and untrained individuals. Am J Physiol 2008; 295: R611-R623
  • 47 Starkie RL, Hargreaves M, Rolland J, Febbraio MA. Heat stress, cytokines, and the immune response to exercise. Brain Behav Immun 2005; 19: 404-412
  • 48 Van Wijck K, Lenaerts K, Van Bijnen AA, Boonen B, Van Loon LJ, Dejong CH, Buurman WA. Aggravation of exercise-induced intestinal injury by Ibuprofen in athletes. Med Sci Sports Exerc 2012; 44: 2257-2262
  • 49 van Wijck K, Lenaerts K, van Loon LJ, Peters WH, Buurman WA, Dejong CH. Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men. PLoS One 2011; 6: e22366