High-intensity exercise training and the immune system: A new role of lactate

Document Type : Review Articles

Authors

Department of Biological Sciences in Sport and Health, Faculty of Sport Sciences and Health, Shahid Beheshti University, Tehran, Iran.

Abstract

High-intensity exercise training is one of the effective strategies to improve the performance of athletes to achieve excellent physical fitness. In the meantime, a look at the history of sports immunology reveals the idea of window theory, which has been of great concern. According to the history of exercise immunology, high-intensity exercise training can suppress the immune system leading to respiratory infections. It has recently been shown that high-intensity exercise training has no effect on suppressing the immune system. In this review, a new perspective on the immune system and high-intensity exercise training was presented to readers. Moreover, a new look at the history of high-intensity exercise training and the immune system and recent review studies was provided and some suggestions are offered.

What is already known on this subject?

Previous studies have shown that exercise can be effective in improving the immune system but inspecting the types of exercise effects on the immune system is still unclear. Moreover, a few studies have reported that lactate can play a very important role in immune response after training. Due to the amount of metabolic stress in different types of exercises, the secretion of lactate is very different and for this reason, investigating the high-intensity interval training effects on the immune system could be useful.

 

What this study adds?

In this review study, we explored the new role of lactate in high-intensity exercise training and its relationship to the immune system. However, we still cannot say with certainty that increasing lactate due to high-intensity exercise training can be beneficial or harmful to improve the functioning of the immune system. Therefore, it is suggested that in future research, researchers study the effect of high-intensity exercise training on lactate levels at different times on the immune system by focusing on lactate and the immune system.

Keywords

Main Subjects


Acknowledgements

None.

Funding

None.

Compliance with ethical standards

Conflict of interest The author declare that she has no conflict of interest.

Ethical approval Not applicable.

Informed consent Not applicable.

Author contributions

Conceptualization: M.F.; Methodology: M.N.; Software: None; Validation: M.F.& N.N.; Formal analysis: None; Investigation: Y.A.&R.P.; Resources: M.F.& S.H.; Data curation: R.P.& S.H; Writing - original draft: M.F.& M.N.; Writing - review & editing: M.F.; Visualization: M.N.; Supervision: M.N.; Project administration: M.F.; Funding acquisition: None.

Agha-Alinejad, H., Ahmadi Hekmatikar, A. H., Ruhee, R. T., Shamsi, M. M., Rahmati, M., Khoramipour, K., & Suzuki, K. (2022). A guide to different intensities of exercise, vaccination, and sports nutrition in the course of preparing elite athletes for the management of upper respiratory infections during the COVID-19 pandemic: A narrative review. International Journal of Environmental Research and Public Health, 19(3), 1888. Doi: https://doi.org/10.3390/ijerph19031888
Ahmadi Hekmatikar, A., Haghshenas, R., & Mohammad Sadeghipor, A. (2019). The effect of carbohydrate supplementation and pure water on interleukin 10, glucose and hematological indexes in male football players. Sport Physiology & Management Investigations, 11(4), 135-145. Doi: http://www.sportrc.ir/&url=http://www.sportrc.ir/article_105715.html?lang=en
Alehossein, P., Taheri, M., Tayefeh Ghahremani, P., Dakhlallah, D., Brown, C. M., Ishrat, T., & Nasoohi, S. (2023). Transplantation of exercise-induced extracellular vesicles as a promising therapeutic approach in ischemic stroke. Translational Stroke Research, 14(2), 211-237. Doi: https://doi.org/10.1007/s12975-022-01025-4
Batatinha, H. P., Lira, F. S., Kruger, K., & Rosa Neto, J. C. (2022). Physical exercise and metabolic reprogramming. Essential Aspects of Immunometabolism in Health and Disease, 235-256. Doi: https://doi.org/10.1007/978-3-030-86684-6_12
Bohn, T., Rapp, S., Luther, N., Klein, M., Bruehl, T. J., Kojima, N., ... & Bopp, T. (2018). Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nature Immunology, 19(12), 1319-1329. Doi: https://doi.org/10.1038/s41590-018-0226-8
Born, D. P., Zinner, C., & Sperlich, B. (2017). The mucosal immune function is not compromised during a period of high-intensity interval training. Is it time to reconsider an old assumption?  Frontiers in Physiology, 8, 485. Doi: https://doi.org/10.3389/fphys.2017.00485
Buchheit, M., & Laursen, P. B. (2013). High-intensity interval training, solutions to the programming puzzle: Part II: Anaerobic energy, neuromuscular load and practical applications. Sports Medicine, 43(10), 927-954. Doi: https://doi.org/10.1007/s40279-013-0066-5
Campbell, J. P., & Turner, J. E. (2018). Debunking the myth of exercise-induced immune suppression: redefining the impact of exercise on immunological health across the lifespan. Frontiers in Immunology, 9, 648. Doi: https://doi.org/10.3389/fimmu.2018.00648
Caslin, H. L., Abebayehu, D., Pinette, J. A., & Ryan, J. J. (2021). Lactate is a metabolic mediator that shapes immune cell fate and function. Frontiers in Physiology, 12, 688485. Doi: https://doi.org/10.3389/fphys.2021.688485
Certo, M., Tsai, C. H., Pucino, V., Ho, P. C., & Mauro, C. (2021). Lactate modulation of immune responses in inflammatory versus tumour microenvironments. Nature Reviews Immunology, 21(3), 151-161. Doi: https://doi.org/10.1038/s41577-020-0406-2
Edge, J., Goodman, C., & Bishop, D. (2006). Very high-intensity interval training with short rest periods decreases muscle buffer capacity. In Proc ECSS Conf Laussane (p. 477). Doi: https://doi.org/10.1113/expphysiol.2012.067603
El Basuini, M. F., Teiba, I. I., Shahin, S. A., Mourad, M. M., Zaki, M. A., Labib, E. M., ... & Dawood, M. A. (2022). Dietary Guduchi (Tinospora cordifolia) enhanced the growth performance, antioxidative capacity, immune response and ameliorated stress-related markers induced by hypoxia stress in Nile tilapia (Oreochromis niloticus). Fish & Shellfish Immunology, 120, 337-344. Doi: https://doi.org/10.1016/j.fsi.2021.12.002
Farhani, F., Shahrbanian, S., Auais, M., Hekmatikar, A. H. A., & Suzuki, K. (2022). Effects of aerobic training on brain plasticity in patients with mild cognitive impairment: a systematic review of randomized controlled trials. Brain Sciences, 12(6), 732. Doi: https://doi.org/10.3390/brainsci12060732
Fasihiyan, M., Taheri, M., Ebrahim, K., & Nourshahi, M. (2022). Review of the effect of different types of exercise on cellular-molecular changes of neurons in the rehabilitation period after ischemic stroke. Razi Journal of Medical Sciences, 29(6), 89-104. Doi: http://rjms.iums.ac.ir/article-1-7141-en.html
Ferguson, B. S., Rogatzki, M. J., Goodwin, M. L., Kane, D. A., Rightmire, Z., & Gladden, L. B. (2018). Lactate metabolism: historical context, prior misinterpretations, and current understanding. European Journal of Applied Physiology, 118, 691-728. Doi: https://doi.org/10.1007/s00421-017-3795-6
Ferreira-Júnior, J. B., Freitas, E. D., & Chaves, S. F. (2020). Exercise: A protective measure or an “open window” for COVID-19? A mini review. Frontiers in Sports and Active Living, 2, 61. Doi: https://doi.org/10.3389/fspor.2020.00061
Fischer, K., Hoffmann, P., Voelkl, S., Meidenbauer, N., Ammer, J., Edinger, M., ... & Kreutz, M. (2007). Inhibitory effect of tumor cell–derived lactic acid on human T cells. Blood, 109(9), 3812-3819. Doi:  https://doi.org/10.1182/blood-2006-07-035972
Gonçalves, C. A. M., Dantas, P. M. S., Dos Santos, I. K., Dantas, M., Da Silva, D. C. P., Cabral, B. G. D. A. T., ... & Júnior, G. B. C. (2020). Effect of acute and chronic aerobic exercise on immunological markers: a systematic review. Frontiers in Physiology, 1602. Doi: https://doi.org/10.3389/fphys.2019.01602
Gottfried, E., Kunz-Schughart, L. A., Ebner, S., Mueller-Klieser, W., Hoves, S., Andreesen, R., ... & Kreutz, M. (2006). Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood, 107(5), 2013-2021. Doi: https://doi.org/10.1182/blood-2005-05-1795
Handzlik, M. K., Shaw, A. J., Dungey, M., Bishop, N. C., & Gleeson, M. (2013). The influence of exercise training status on antigen-stimulated IL-10 production in whole blood culture and numbers of circulating regulatory T cells. European Journal of Applied Physiology, 113, 1839-1848. Doi: https://doi.org/10.1007/s00421-013-2614-y
Hawley, J. A., Hargreaves, M., Joyner, M. J., & Zierath, J. R. (2014). Integrative biology of exercise. Cell, 159(4), 738-749. Doi: https://doi.org/10.1016/j.cell.2014.10.029
Hooshmand Moghadam, B., Golestani, F., Bagheri, R., Cheraghloo, N., Eskandari, M., Wong, A., ... & Pournemati, P. (2021). The effects of high-intensity interval training vs. moderate-intensity continuous training on inflammatory markers, body composition, and physical fitness in overweight/obese survivors of breast cancer: a randomized controlled clinical trial. Cancers, 13(17), 4386. Doi: https://doi.org/10.3390/cancers13174386
Hotchkiss, R. S., Monneret, G., & Payen, D. (2013). Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nature Reviews Immunology, 13(12), 862-874. Doi: https://doi.org/10.1038/nri3552
Improta-Caria, A. C., Soci, Ú. P. R., Pinho, C. S., Aras Júnior, R., De Sousa, R. A. L., & Bessa, T. C. B. (2021). Physical exercise and immune system: perspectives on the COVID-19 pandemic. Revista da Associação Médica Brasileira, 67, 102-107. Doi: https://doi.org/10.1590/1806-9282.67.Suppl1.20200673
Kakanis, M., Peake, J., Hooper, S., Gray, B., & Marshall-Gradisnik, S. (2010). The open window of susceptibility to infection after acute exercise in healthy young male elite athletes. Journal of Science and Medicine in Sport, 13, e85-e86. Doi: https://doi.org/10.1016/j.jsams.2010.10.642
Kaspar, F., Jelinek, H. F., Perkins, S., Al-Aubaidy, H. A., Dejong, B., & Butkowski, E. (2016). Acute-phase inflammatory response to single-bout HIIT and endurance training: a comparative study. Mediators of Inflammation, 2016. Doi: https://doi.org/10.1155/2016/5474837
Kazemi, A., & Ahmadi Hekmatikar, A. H. (2023). Aging, immune system, and physical activity: A review of recent studies. Journal of Exercise & Organ Cross Talk, 3(1), 29-42. Doi: https://doi.org/10.22034/jeoct.2023.381226.1063
Khalafi, M., & Symonds, M. E. (2020). The impact of high‐intensity interval training on inflammatory markers in metabolic disorders: A meta‐analysis. Scandinavian Journal of Medicine & Science in Sports, 30(11), 2020-2036. Doi: https://doi.org/10.1111/sms.13754
Khammassi, M., Ouerghi, N., Said, M., Feki, M., Khammassi, Y., Pereira, B., ... & Bouassida, A. (2020). Continuous moderate-intensity but not high-intensity interval training improves immune function biomarkers in healthy young men. The Journal of Strength & Conditioning Research, 34(1), 249-256. Doi: https://doi.org/10.1519/JSC.0000000000002737
Khoramipour, K., Hekmatikar, A. A., & Sotvan, H. (2020). An overview of Fatmax and MFO in exercise. Razi J. Med. Sci, 27, 49-59. Doi: http://rjms.iums.ac.ir/article-1-5959-en.html
Laine, M. K., Eriksson, J. G., Kujala, U. M., Kaprio, J., Loo, B. M., Sundvall, J., ... & Sarna, S. (2016). Former male elite athletes have better metabolic health in late life than their controls. Scandinavian Journal of Medicine & Science in Sports, 26(3), 284-290. Doi: https://doi.org/10.1111/sms.12442
Liu, D., Wang, R., Grant, A. R., Zhang, J., Gordon, P. M., Wei, Y., & Chen, P. (2017). Immune adaptation to chronic intense exercise training: new microarray evidence. BMC Genomics, 18(1), 1-10. Doi: https://doi.org/10.1186/s12864-016-3388-5
Mackinnon, L. T. (1999). Advances in exercise immunology. Human Kinetics.
Manoharan, I., Prasad, P. D., Thangaraju, M., & Manicassamy, S. (2021). Lactate-dependent regulation of immune responses by dendritic cells and macrophages. Frontiers in Immunology, 12, 691134. Doi: https://doi.org/10.3389/fimmu.2021.691134
Medbø, J. I. (1993). Glycogen breakdown and lactate accumulation during high‐intensity cycling. Acta Physiologica Scandinavica, 149(1), 85-89. Doi: https://doi.org/10.1111/j.1748-1716.1993.tb09595.x
Nasi, A., & Rethi, B. (2013). Disarmed by density: A glycolytic break for immunostimulatory dendritic cells? Oncoimmunology, 2(12), e26744. Doi: https://doi.org/10.4161/onci.26744
Nieman, D. C., & Wentz, L. M. (2019). The compelling link between physical activity and the body's defense system. Journal of Sport and Health Science, 8(3), 201-217. Doi: https://doi.org/10.1016/j.jshs.2018.09.009
Ohkuwa, T., Kato, Y., Katsumata, K., Nakao, T., & Miyamura, M. (1984). Blood lactate and glycerol after 400-m and 3,000-m runs in sprint & long distance runners. European Journal of Applied physiology
and Occupational Physiology, 53, 213-218. Doi: https://doi.org/10.1007/BF00776592
Peake, J. M., Neubauer, O., Walsh, N. P., & Simpson, R. J. (2017). Recovery of the immune system after exercise. Journal of Applied Physiology, 122(5), 1077-1087. Doi: https://doi.org/10.1152/japplphysiol.00622.2016
Pérez-Martínez, D. (2016). Innate immunity in vertebrates: An overview. Immunology, 148(2), 125-139. Doi: https://doi.org/10.1111/imm.12597
Ratter, J. M., Rooijackers, H. M., Hooiveld, G. J., Hijmans, A. G., De Galan, B. E., Tack, C. J., & Stienstra, R. (2018). In vitro and in vivo effects of lactate on metabolism and cytokine production of human primary PBMCs and monocytes. Frontiers in Immunology, 9, 2564. Doi: https://doi.org/10.3389/fimmu.2018.02564
Sellami, M., Gasmi, M., Denham, J., Hayes, L. D., Stratton, D., Padulo, J., & Bragazzi, N. (2018). Effects of acute and chronic exercise on immunological parameters in the elderly aged: can physical activity counteract the effects of aging? Frontiers in Immunology, 9, 2187. Doi: https://doi.org/10.3389/fimmu.2018.02187
Simpson, R. J., Campbell, J. P., Gleeson, M., Krüger, K., Nieman, D. C., Pyne, D. B., ... & Walsh, N. P. (2020). Can exercise affect immune function to increase susceptibility to infection? Exercise Immunology Review,26, 8-22. Doi: https://www.ncbi.nlm.nih.gov/pubmed/32139352
Souza, D., Vale, A. F., Silva, A., Araújo, M. A. S., de Paula Júnior, C. A., de Lira, C. A. B., ... & Gentil, P. (2021). Acute and chronic effects of interval training on the immune system: A systematic review with meta-analysis. Biology 2021, 10, 868. Doi: https://doi.org/10.3390/biology10090868
Tayebi, S. M., Hekmatikar, A. A., Ghanbari-Niaki, A., & Fathi, R. (2020). Ghrelin behavior in exercise and training. J Med. Sci, 27, 85-111. Doi: http://rjms.iums.ac.ir/article-1-5803-en.html
Terra, R., Silva, S. A. G. D., Pinto, V. S., & Dutra, P. M. L. (2012). Effect of exercise on immune system: response, adaptation and cell signaling. Revista brasileira de medicina do esporte, 18, 208-214. Doi: https://doi.org/10.1590/S1517-86922012000300015
Walsh, N. P., Gleeson, M., Pyne, D. B., Nieman, D. C., Dhabhar, F. S., Shephard, R. J., ... & Kajeniene, A. (2011). Position statement part two: maintaining immune health.
Watts, E. R., & Walmsley, S. R. (2019). Inflammation and hypoxia: HIF and PHD isoform selectivity. Trends in Molecular Medicine, 25(1), 33-46. Doi: https://doi.org/10.1016/j.molmed.2018.10.006
Zhang, L., & Li, S. (2020). Lactic acid promotes macrophage polarization through MCT-HIF1α signaling in gastric cancer. Experimental Cell Research, 388(2), 111846. Doi: https://doi.org/10.1016/j.yexcr.2020.111846