Exercise and Inflammatory Response: Mechanism of Interleukin-6 Expression Changes

Authors

  • Delvy Atriani Universitas Sriwijaya
  • Irfannuddin Irfannuddin Universitas Sriwijaya
  • Budi Santoso Universitas Sriwijaya

DOI:

https://doi.org/10.37287/ijghr.v8i2.1548

Keywords:

cytokine, exercise, exercise adaptation, interleukin-6

Abstract

Exercise has a broad impact on health through various physiological mechanisms, one of which is through the regulation of interleukin-6 (IL-6). IL-6 is a pleiotropic cytokine that plays a role in immune responses, inflammation, and energy metabolism regulation, and is produced not only by immune cells but also by skeletal muscle as myokine during physical activity. This article aims to examine the physiological adaptations of exercise to IL-6 production and function and its relationship to energy metabolism, mitochondrial function, and inflammatory response. The research method employed was a literature review utilizing a descriptive approach. In acute exercise, muscle contraction triggers a rapid and temporary increase in IL-6 through mechanisms involving changes in calcium homeostasis, activation of AMP-activated protein kinase (AMPK) due to decreased energy reserves, oxidative stress, and epigenetic regulation. This study was conducted using a descriptive literature review approach. Relevant primary research articles and review papers were systematically identified through electronic databases, the selected literature was analyzed and synthesized to explore the mechanisms underlying exercise-induced changes in Interleukin-6 (IL-6) expression and signaling, with particular emphasis on acute and chronic exercise adaptations, energy metabolism, mitochondrial function, and inflammatory responses. The increase in IL-6 during this phase plays a role in maintaining energy homeostasis by increasing glucose transport, fatty acid oxidation, and modulating the immune response. Conversely, regular exercise induces long-term adaptations in the form of increased mitochondrial number and function, increased antioxidant capacity, and increased muscle sensitivity to IL-6 through the classical signaling pathway. These adaptations enhance IL-6 signaling efficiency, enabling metabolic and anti-inflammatory responses to be achieved with lower IL-6 production. Thus, regular exercise plays a crucial role in reducing systemic inflammation, improving energy metabolism, and supporting health and the prevention of chronic diseases.

References

Abbas, Abdul K., Lichtman, Andrew H., P. (2022). Cellular And Molecular Immunology TENth Edition. Antimicrobial Agents and Chemotherapy, 58(12).

Abu-Omar, K., Chevance, G., Tcymbal, A., Gelius, P., & Messing, S. (2023). Physical activity promotion, human and planetary health – a conceptual framework and suggested research priorities. Journal of Climate Change and Health, 13. https://doi.org/10.1016/j.joclim.2023.100262

AL-Mhanna, S. B., Ghazali, W. S. W., Mohamed, M., Rabaan, A. A., Santali, Eman Y., Alestad, J. H., Santali, Enas Y., Arshad, S., Ahmed, N., & Afolabi, H. A. (2022). Effectiveness of physical activity on immunity markers and quality of life in cancer patient: a systematic review. In PeerJ (Vol. 10). https://doi.org/10.7717/peerj.13664

Berg, R. M. G. (2025). The enduring quest for an ‘exercise factor’: A historical account of skeletal muscle as an endocrine organ. In Journal of Physiology. https://doi.org/10.1113/JP289744

Boulanger, M. J., Chow, D. chone, Brevnova, E. E., & Garcia, K. C. (2003). Hexameric structure and assembly of the interieukin-6/IL-6 α-receptor/gp130 complex. Science, 300(5628). https://doi.org/10.1126/science.1083901

Dimitri, P., Joshi, K., & Jones, N. (2020). Moving more: physical activity and its positive effects on long term conditions in children and young people. In Archives of Disease in Childhood (Vol. 105, Number 11). https://doi.org/10.1136/archdischild-2019-318017

Docherty, S., Harley, R., McAuley, J. J., Crowe, L. A. N., Pedret, C., Kirwan, P. D., Siebert, S., & Millar, N. L. (2022). The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review. In BMC Sports Science, Medicine and Rehabilitation (Vol. 14, Number 1). https://doi.org/10.1186/s13102-022-00397-2

Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., & Guzik, P. (2021a). Effect of various exercise regimens on selected exercise-induced cytokines in healthy people. In International Journal of Environmental Research and Public Health (Vol. 18, Number 3). https://doi.org/10.3390/ijerph18031261

Fischer, C. P. (2006). Interleukin-6 in acute exercise and training: What is the biological relevance? In Exercise Immunology Review (Vol. 12).

Hunter, D. J., James, L. S., Hussey, B., Ferguson, R. A., Lindley, M. R., & Mastana, S. S. (2023). Impacts of Eccentric Resistance Exercise on DNA Methylation of Candidate Genes for Inflammatory Cytokines in Skeletal Muscle and Leukocytes of Healthy Males. Genes, 14(2). https://doi.org/10.3390/genes14020478

Islam, H., Tsai, S. H., Figueiredo, C., Jackson, G. S., Marcotte-Chénard, A., Bosak, J., Moreno-Cabañas, A., Lira, F. S., & Little, J. P. (2024). Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity-dependent reductions in anti-inflammatory cytokine action. Journal of Physiology, 602(12). https://doi.org/10.1113/JP286228

Kistner, T. M., Trinh, B., Mfeketo, K., van Hall, G., Pedersen, B. K., Lieberman, D. E., & Ellingsgaard, H. (2026). Myokine IL-6 activity enhances post-exercise fatty acid accumulation in skeletal muscle but does not affect glycogen resynthesis. Molecular Metabolism, 103. https://doi.org/10.1016/j.molmet.2025.102283

Li, J., Wang, Z., Li, C., Song, Y., Wang, Y., Bo, H., & Zhang, Y. (2022). Impact of Exercise and Aging on Mitochondrial Homeostasis in Skeletal Muscle: Roles of ROS and Epigenetics. In Cells (Vol. 11, Number 13). https://doi.org/10.3390/cells11132086

Liu, X., Wang, X., & Wang, T. (2024). Evaluation of the Impact of Long-term Treadmill Exercise on Antioxidant Capacity and Immune Function in Mice. Kafkas Universitesi Veteriner Fakultesi Dergisi, 30(1). https://doi.org/10.9775/kvfd.2023.30826

Małkowska, P., & Sawczuk, M. (2023). Cytokines as Biomarkers for Evaluating Physical Exercise in Trained and Non-Trained Individuals: A Narrative Review. In International Journal of Molecular Sciences (Vol. 24, Number 13). https://doi.org/10.3390/ijms241311156

Nash, D., Hughes, M. G., Butcher, L., Aicheler, R., Smith, P., Cullen, T., & Webb, R. (2023). IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance. In Scandinavian Journal of Medicine and Science in Sports (Vol. 33, Number 1). https://doi.org/10.1111/sms.14241

Okely, A. D., Kontsevaya, A., Ng, J., & Abdeta, C. (2021). 2020 WHO guidelines on physical activity and sedentary behavior. In Sports Medicine and Health Science (Vol. 3, Number 2). https://doi.org/10.1016/j.smhs.2021.05.001

Park, S.-T. (2023). Physical Activity and Immunity in the Elderly for the Post-COVID-19 Pandemic Era: A Literature Review. The Asian Journal of Kinesiology, 25(4), 50–59. https://doi.org/10.15758/ajk.2023.25.4.50

Poorhabibi, H., Weiss, K., Rosemann, T., Knechtle, B., Eslami, R., Tartibian, B., Tayebi, S. M., & Sheikhhoseini, R. (2025). Short-Lived Exercise-Induced Exerkines Modulate Inflammation for Chronic Disease Prevention: A Systematic Review and Meta-Analysis. In Biomolecules (Vol. 15, Number 11). https://doi.org/10.3390/biom15111590

Reddy, H., Javvaji, C. K., Malali, S., Kumar, S., Acharya, S., & Toshniwal, S. (2024). Navigating the Cytokine Storm: A Comprehensive Review of Chemokines and Cytokines in Sepsis. Cureus. https://doi.org/10.7759/cureus.54275

Stenken, J. A., & Poschenrieder, A. J. (2015). Bioanalytical chemistry of cytokines - A review. In Analytica Chimica Acta (Vol. 853, Number 1, pp. 95–115). Elsevier B.V. https://doi.org/10.1016/j.aca.2014.10.009

Światowy, W. J., Drzewiecka, H., Kliber, M., Sąsiadek, M., Karpiński, P., Pławski, A., & Jagodziński, P. P. (2021). Physical activity and DNA methylation in humans. In International Journal of Molecular Sciences (Vol. 22, Number 23). https://doi.org/10.3390/ijms222312989

Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). Il-6 in inflammation, Immunity, And disease. Cold Spring Harbor Perspectives in Biology, 6(10). https://doi.org/10.1101/cshperspect.a016295

Ting, E. Y. C., Yang, A. C., & Tsai, S. J. (2020). Role of interleukin-6 in depressive disorder. In International Journal of Molecular Sciences (Vol. 21, Number 6). MDPI AG. https://doi.org/10.3390/ijms21062194

Villar-Fincheira, P., Sanhueza-Olivares, F., Norambuena-Soto, I., Cancino-Arenas, N., Hernandez-Vargas, F., Troncoso, R., Gabrielli, L., & Chiong, M. (2021). Role of Interleukin-6 in Vascular Health and Disease. In Frontiers in Molecular Biosciences (Vol. 8). https://doi.org/10.3389/fmolb.2021.641734

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Published

2026-03-24

How to Cite

Atriani, D., Irfannuddin, I., & Santoso, B. (2026). Exercise and Inflammatory Response: Mechanism of Interleukin-6 Expression Changes. Indonesian Journal of Global Health Research, 8(2), 905–912. https://doi.org/10.37287/ijghr.v8i2.1548