Skip to main content

Pro- and anti-inflammatory cytokine responses to a 164-km road cycle ride in a hot environment

European Journal of Applied Physiology volume 116, pages 2007–2015 (2016)Cite this article

Abstract

Purpose

The purpose of this study was to examine the circulating cytokine response to a recreational 164-km road cycling event in a high ambient temperature and to determine if this response was affected by self-paced exercise time to completion.

Methods

Thirty-five men and five women were divided into tertiles based on time to complete the cycling event: slowest (SLOW), moderate (MOD), and fastest (FAST) finishers. Plasma samples were obtained 1–2 h before (PRE) and immediately after (IP) the event. A high-sensitivity multiplex assay kit was used to determine the concentration of plasma anti-inflammatory cytokines (IL-4, IL-5, IL-10, IL-13) and pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-7, IL-8, IL-12, GM-CSF, IFN-γ, and TNF-α).

Results

The concentration of plasma IL-10 increased significantly (p < 0.05) in FAST and MOD groups and had no change in the SLOW group in response to a 164-km cycling event in the hot environment. Other cytokine responses were not influenced by the Time to completion. Pro-inflammatory cytokines IL-1β, IL-2, GM-CSF, and TNF-α decreased; whereas, IL-6 and IL-8 increased from PRE to IP. Additionally, anti-inflammatory cytokines IL-4 and IL-13 decreased.

Conclusions

Completion of a 164-km cycling event induced substantial changes in circulating pro- and anti-inflammatory cytokine concentrations. Time to completion appears to have a greater influence on the systemic IL-10 response than the environmental condition; however, it is possible that a threshold for absolute intensity must be reached for environmental conditions to affect the IL-10 response to exercise. Thus, cyclists from the FAST/MOD groups appear more likely to experience an acute transient immune suppression than cyclists from the SLOW group.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1

Abbreviations

ANOVA:

Analysis of variance

GM-CSF:

Granulocyte macrophage colony-stimulating factor

IFN:

Interferon

IL:

Interleukin

IP:

Immediately after the 164-km cycling event

PRE:

Approximately 1–2 h before the 164-km cycling event

TNF:

Tumor necrosis factor

References

  • Armstrong LE, Casa DJ, Emmanuel H et al (2012) Nutritional, physiological, and perceptual responses during a summer ultraendurance cycling event. J Strength Cond Res 26:307–318. doi:10.1519/JSC.0b013e318240f677

    Article  PubMed  Google Scholar 

  • Blotta MH, DeKruyff RH, Umetsu DT (1997) Corticosteroids inhibit IL-12 production in human monocytes and enhance their capacity to induce IL-4 synthesis in CD4+ lymphocytes. J Immunol 158:5589–5595

    CAS  PubMed  Google Scholar 

  • Bury TB, Louis R, Radermecker MF, Pirnay F (1996) Blood mononuclear cells mobilization and cytokines secretion during prolonged exercises. Int J Sports Med 17:156–160. doi:10.1055/s-2007-972825

    CAS  Article  PubMed  Google Scholar 

  • Carpenter KC, Breslin WL, Davidson T, Adams A, McFarlin BK (2013) Baker’s yeast beta-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk? Br J Nutr 109:478–486. doi:10.1017/S0007114512001407

    CAS  Article  PubMed  Google Scholar 

  • Castell LM, Poortmans JR, Leclercq R, Brasseur M, Duchateau J, Newsholme EA (1997) Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation. Eur J Appl Physiol Occup Physiol 75:47–53

    CAS  Article  PubMed  Google Scholar 

  • Clarke CJ, Hales A, Hunt A, Foxwell BM (1998) IL-10-mediated suppression of TNF-alpha production is independent of its ability to inhibit NF kappa B activity. Eur J Immunol 28:1719–1726. doi:10.1002/(SICI)1521-4141(199805)28:053.0.CO;2-Q

    CAS  Article  PubMed  Google Scholar 

  • Cosio-Lima LM, Desai BV, Schuler PB, Keck L, Scheeler L (2011) A comparison of cytokine responses during prolonged cycling in normal and hot environmental conditions. Open Access J Sports Med 2:7

    Article  PubMed  PubMed Central  Google Scholar 

  • da Fonseca-Engelhardt K, Knechtle B, Rust CA, Knechtle P, Lepers R, Rosemann T (2013) Participation and performance trends in ultra-endurance running races under extreme conditions—’Spartathlon’ versus ‘Badwater’. Extrem Physiol Med 2:15-7648-2-15. doi:10.1186/2046-7648-2-15

  • DeKruyff RH, Fang Y, Umetsu DT (1998) Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 160:2231–2237

    CAS  PubMed  Google Scholar 

  • Dinarello CA (2000) Proinflammatory cytokines. Chest 118:503–508

    CAS  Article  PubMed  Google Scholar 

  • Elenkov IJ, Chrousos GP (1999) Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. Trends Endocrinol Metab 10:359–368

    CAS  Article  PubMed  Google Scholar 

  • Elenkov IJ, Chrousos GP (2002) Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 966:290–303

    CAS  Article  PubMed  Google Scholar 

  • Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP (2005) Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12:255–269

    CAS  Article  PubMed  Google Scholar 

  • Gannon GA, Rhind SG, Suzui M, Shek PN, Shephard RJ (1997) Circulating levels of peripheral blood leucocytes and cytokines following competitive cycling. Can J Appl Physiol 22:133–147

    CAS  Article  PubMed  Google Scholar 

  • Hetier E, Ayala J, Bousseau A, Prochiantz A (1991) Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res 86:407–413

    CAS  Article  PubMed  Google Scholar 

  • Kraemer WJ, Fragala MS, Watson G et al (2008) Hormonal responses to a 160-km race across frozen Alaska. Br J Sports Med 42:116–120. doi:10.1136/bjsm.2007.035535 (Discussion 120)

  • Kupchak BR, McKenzie AL, Luk HY et al (2015) Effect of cycling in the heat for 164 km on procoagulant and fibrinolytic parameters. Eur J Appl Physiol 115:1295–1303. doi:10.1007/s00421-015-3107-y

    CAS  Article  PubMed  Google Scholar 

  • Lalani I, Bhol K, Ahmed AR (1997) Interleukin-10: biology, role in inflammation and autoimmunity. Ann Allergy Asthma Immunol 79:469–483

    CAS  Article  PubMed  Google Scholar 

  • Leng SX, McElhaney JE, Walston JD, Xie D, Fedarko NS, Kuchel GA (2008) ELISA and multiplex technologies for cytokine measurement in inflammation and aging research. J Gerontol A Biol Sci Med Sci 63:879–884

    Article  PubMed  PubMed Central  Google Scholar 

  • Levin TC, Wickliffe KE, Leppla SH, Moayeri M (2008) Heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin. Cell Microbiol 10:2434–2446. doi:10.1111/j.1462-5822.2008.01220.x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Moore KW, O’Garra A, de Waal Malefyt R, Vieira P, Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–190. doi:10.1146/annurev.iy.11.040193.001121

    CAS  Article  PubMed  Google Scholar 

  • Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17:701–738. doi:10.1146/annurev.immunol.17.1.701

    CAS  Article  PubMed  Google Scholar 

  • Nieman DC (1994) Exercise, upper respiratory tract infection, and the immune system. Med Sci Sports Exerc 26:128–139

    CAS  Article  PubMed  Google Scholar 

  • Nieman DC, Nehlsen-Cannarella SL, Fagoaga OR et al (2000) Immune function in female elite rowers and non-athletes. Br J Sports Med 34:181–187

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Nieman DC, Henson DA, Smith LL et al (2001) Cytokine changes after a marathon race. J Appl Physiol (1985) 91:109–114

    CAS  Google Scholar 

  • Nieman DC, Dumke CL, Henson DA, McAnulty SR, Gross SJ, Lind RH (2005) Muscle damage is linked to cytokine changes following a 160-km race. Brain Behav Immun 19:398–403. doi:10.1016/j.bbi.2005.03.008

    CAS  Article  PubMed  Google Scholar 

  • Nieman DC, Konrad M, Henson DA, Kennerly K, Shanely RA, Wallner-Liebmann SJ (2012) Variance in the acute inflammatory response to prolonged cycling is linked to exercise intensity. J Interferon Cytokine Res 32:12–17. doi:10.1089/jir.2011.0038

    CAS  Article  PubMed  Google Scholar 

  • Northoff H, Berg A, Weinstock C (1998) Similarities and differences of the immune response to exercise and trauma: the IFN-gamma concept. Can J Physiol Pharmacol 76:497–504

    CAS  Article  PubMed  Google Scholar 

  • Opal SM, DePalo VA (2000) Anti-inflammatory cytokines. Chest 117:1162–1172

    CAS  Article  PubMed  Google Scholar 

  • Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK (1999) Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 515(Pt 1):287–291

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Peake JM, Suzuki K, Hordern M, Wilson G, Nosaka K, Coombes JS (2005) Plasma cytokine changes in relation to exercise intensity and muscle damage. Eur J Appl Physiol 95:514–521. doi:10.1007/s00421-005-0035-2

    CAS  Article  PubMed  Google Scholar 

  • Peake J, Peiffer JJ, Abbiss CR et al (2008) Body temperature and its effect on leukocyte mobilization, cytokines and markers of neutrophil activation during and after exercise. Eur J Appl Physiol 102:391–401. doi:10.1007/s00421-007-0598-1

    CAS  Article  PubMed  Google Scholar 

  • Pistilli EE, Nieman DC, Henson DA et al (2002) Influence of age on immune changes in runners after a marathon. J Aging Phys Act 10:432–442

    Article  Google Scholar 

  • Rhind SG, Gannon GA, Shephard RJ, Buguet A, Shek PN, Radomski MW (2004) Cytokine induction during exertional hyperthermia is abolished by core temperature clamping: neuroendocrine regulatory mechanisms. Int J Hyperth 20:503–516. doi:10.1080/02656730410001670651

    CAS  Article  Google Scholar 

  • Severn A, Rapson NT, Hunter CA, Liew FY (1992) Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J Immunol 148:3441–3445

    CAS  PubMed  Google Scholar 

  • Shephard RJ, Rhind S, Shek PN (1994) Exercise and training: influences on cytotoxicity, interleukin-1, interleukin-2 and receptor structures. Int J Sports Med 15(Suppl 3):S154–S166. doi:10.1055/s-2007-1021131

    Article  PubMed  Google Scholar 

  • Shin YO, Lee JB (2012) Leukocyte chemotactic cytokine and leukocyte subset responses during ultra-marathon running. Cytokine

  • Starkie RL, Hargreaves M, Rolland J, Febbraio MA (2005) Heat stress, cytokines, and the immune response to exercise. Brain Behav Immun 19:404–412

    CAS  Article  PubMed  Google Scholar 

  • Suzuki K, Yamada M, Kurakake S et al (2000) Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans. Eur J Appl Physiol 81:281–287

    CAS  Article  PubMed  Google Scholar 

  • Suzuki K, Nakaji S, Yamada M, Totsuka M, Sato K, Sugawara K (2002) Systemic inflammatory response to exhaustive exercise. Cytokine kinetics. Exerc Immunol Rev 8:6–48

    PubMed  Google Scholar 

  • Suzuki K, Nakaji S, Yamada M et al (2003) Impact of a competitive marathon race on systemic cytokine and neutrophil responses. Med Sci Sports Exerc 35:348–355. doi:10.1249/01.MSS.0000048861.57899.04

    CAS  Article  PubMed  Google Scholar 

  • Svendsen IS, Killer SC, Gleeson M (2014) Influence of hydration status on changes in plasma cortisol, leukocytes and antigen-stimulated cytokine production by whole blood culture following prolonged exercise

  • Tuttle JA, Castle PC, Metcalfe AJ, Midgley AW, Taylor L, Lewis MP (2015) Downhill running and exercise in hot environments increase leukocyte Hsp72 (HSPA1A) and Hsp90alpha (HSPC1) gene transcripts. J Appl Physiol (1985) 118:996–1005. doi:10.1152/japplphysiol.00387.2014

    CAS  Article  Google Scholar 

  • van der Poll T, Lowry SF (1997) Lipopolysaccharide-induced interleukin 8 production by human whole blood is enhanced by epinephrine and inhibited by hydrocortisone. Infect Immun 65:2378–2381

    PubMed  PubMed Central  Google Scholar 

  • van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF (1996) Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 97:713–719. doi:10.1172/JCI118469

    Article  PubMed  PubMed Central  Google Scholar 

  • Vingren JL, Budnar Jr RG, McKenzie AL et al (2015) The acute testosterone, growth hormone, cortisol and interleukin-6 response to 164-km road cycling in a hot environment. J Sports Sci 1–6

  • Weinstock C, Konig D, Harnischmacher R, Keul J, Berg A, Northoff H (1997) Effect of exhaustive exercise stress on the cytokine response. Med Sci Sports Exerc 29:345–354

    CAS  Article  PubMed  Google Scholar 

  • Zaldivar F, Wang-Rodriguez J, Nemet D et al (2006) Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes. J Appl Physiol (1985) 100:1124–1133

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Applied Physiology Laboratory, Department of Kinesiology, Health Promotion, and Recreation, University of North Texas, 1155 Union Circle #310769, Denton, TX, 76203-5017, USA

    Hui-Ying Luk, Danielle E. Levitt, Brian K. McFarlin, David W. Hill & Jakob L. Vingren

  2. Department of Biological Sciences, University of North Texas, 1155 Union Circle #305220, Denton, TX, 76203-5017, USA

    Hui-Ying Luk, Danielle E. Levitt, Brian K. McFarlin & Jakob L. Vingren

  3. Human Performance Laboratory, Department of Kinesiology, University of Connecticut, Storrs, CT, 06269, USA

    Elaine C. Lee & Lawrence E. Armstrong

  4. Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, 72701, USA

    Matthew S. Ganio & Brendon P. McDermott

  5. Department of Military and Emergency Medicine, Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA

    Brian R. Kupchak

Authors
  1. Hui-Ying Luk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Danielle E. Levitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elaine C. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthew S. Ganio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Brendon P. McDermott
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brian R. Kupchak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brian K. McFarlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David W. Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lawrence E. Armstrong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jakob L. Vingren
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jakob L. Vingren.

Ethics declarations

Funding

This research study was not funded by external sources; all funds were internal to the University of Connecticut or University of North Texas.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the Institutional Review Board of the University of Connecticut and in accordance with the 1964 Helsinki declaration and its later amendments. This article does not contain any studies with animals performed by the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Disclaimer

The opinions and assertions expressed herein are those of the authors and should not be constructed as reflecting those of the Uniformed Services University, Department of the Army, Department of the Air Force, Department of the Navy or the United States Department of Defense.

Additional information

Communicated by Fabio Fischetti.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Luk, HY., Levitt, D.E., Lee, E.C. et al. Pro- and anti-inflammatory cytokine responses to a 164-km road cycle ride in a hot environment. Eur J Appl Physiol 116, 2007–2015 (2016). https://doi.org/10.1007/s00421-016-3452-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-016-3452-5

Keywords

  • Pro-inflammatory cytokine
  • Anti-inflammatory cytokine
  • Immune suppression
  • Heat
  • Ultra-endurance
  • Exercise