Cytokines are secreted proteins that influence the survival, proliferation, differentiation and function of immune cells and other organ systems (Alexander, 2002). Cytokines can be secreted by a variety of cells including neutrophils, activated macrophages, fibroblasts, endothelial cells and damaged muscle cells (Cannon & Pierre, 1998). Indeed, the muscle itself can also release cytokines as a result of motor unit contractions. For example it has been a consistent finding that interleukin 6 (IL-6) increases by several folds in response to endurance exercise (Pedersen & Febbraio, 2008). The below table shows many different cytokine characteristics and actions.
Calle & Fernandez (2010)
Physical exercise is associated with muscle cell injury and, hence, the synthesis of anti-inflammatory cytokines (IL-6 and IL-10), from the bone marrow into the bloodstream, in balance with proinflammatory cytokines (TNF-α and IL-1Ra). IL-6 has an important function in this muscle repair, since it increases soon after the beginning of the exercise and promotes anti-inflammatory actions and also inhibitory effects on the production and secretion of TNF-α (mainly), which cause a chronic adaptation to exercise (Cordova, et. al., 2011).
Pereira et al. (2013) investigated the effects of a single resistance training (RT) session on the serum concentrations of cytokines (TNF-α, IL-1a, IL-1b, IL-12, IL-6, and IL-10) in women with metabolic syndrome. No statistical difference was observed; however, there was a trend to decrease TNF-α concentration and to increase IL-1b and IL-6 concentrations 60 minutes after the training. This result indicates that a single RT session can modulate and reduce proinflammatory cytokines and shows that periodized and systematized training programs have a positive effect on cytokine concentrations. Rossetti et al. (2009) explain that RT releases myokines (cytokines produced in active muscles), particularly IL-6, stimulating the production of anti-inflammatory cytokines (IL-6 and IL-10), which in turn inhibit the production of the proinflammatory cytokine (TNF-α). This process occurs in acute and consecutive training sessions and supports the systemic decrease in serum concentrations of total cytokines and, hence, in the acute inflammatory marker (CRP) (Pedersen & Fischer, 2007).
Córdova et al. (2011), investigated the association between eight weeks of RT and serum concentrations of IL-6, TNF-α, and IFN-γ in elderly women. The study demonstrated that RT in elderly women is associated with low serum concentrations of proinflammatory cytokines, evidenced the impact of RT on these markers, and showed that sedentary lifestyle is a risk factor for diseases related to the aging process. Ho et al. (2013) observed the effects of 12 weeks of training on inflammatory markers TNF-α, IL-6, and CRP in overweight and obese individuals and reinforced that idea because all studied variables decreased in the training group compared with the control.
This review has discussed the cytokine responses after an acute bout of RT and after long term RT in healthy individuals. The majority of the studies reported an increase in the response to an acute bout of RT on specifically the anti-inflammatory IL-10 and IL-6. There are differences in cytokine responses to long term RT depending on the time intervals during sampling and if the comparisons with pre and post-training are at rest or after the acute bout of RT. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise (Calle & Fernandez 2010).
Thus, more research is needed in the area of RT in healthy populations. Specifically, determining gender and age RT responses, and more importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases.
References
Alexander, W.S. (2002). Suppressors of cytokine signaling (SOCS) in the immune system. Nat Rev Immunol. 2, 410-6.
Calle, M. C., & Fernandez, M. L. (2010). Effects of resistance training on the inflammatory response. Nutrition research and practice, 4(4), 259–269. https://doi.org/10.4162/nrp.2010.4.4.259
Cannon, J. G., & Pierre, B. A. S. (1998). Cytokines in exertion-induced skeletal muscle injury. Molecular and cellular biochemistry, 179(1-2), 159-168.
Córdova, C., Lopes-e-Silva Jr, F., Pires, A. S., Souza, V. C., Brito, C. J., Moraes, C. F., … & Nóbrega, O. T. (2011). Long-term resistance training is associated with reduced circulating levels of IL-6, IFN-gamma and TNF-alpha in elderly women. Neuroimmunomodulation, 18(3), 165-170.
Ho, S. S., Dhaliwal, S. S., Hills, A. P., & Pal, S. (2013). Effects of chronic exercise training on inflammatory markers in Australian overweight and obese individuals in a randomized controlled trial. Inflammation, 36(3), 625-632.
Pedersen, B. K., & Febbraio, M. A. (2008). Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiological reviews.
Pedersen, B. K., & Fischer, C. P. (2007). Beneficial health effects of exercise–the role of IL-6 as a myokine. Trends in pharmacological sciences, 28(4), 152-156.
Pereira, G. B., Tibana, R. A., Navalta, J., Sousa, N. M., Córdova, C., Souza, V. C., … & Perez, S. E. (2013). Acute effects of resistance training on cytokines and osteoprotegerin in women with metabolic syndrome. Clinical Physiology and Functional Imaging, 33(2), 122-130.
Rossetti, M. B., Britto, R. R., & Norton, R. D. C. (2009). Early prevention of cardiovascular diseases in juvenile obesity: The anti-inflammatory effect of physical exercise. Revista Brasileira de Medicina do Esporte, 15(6), 472-475.
Santiago, L. Â. M., Neto, L. G. L., Pereira, G. B., Leite, R. D., Mostarda, C. T., Monzani, J. D. O. B., … & Navarro, F. (2018). Effects of resistance training on immunoinflammatory response, TNF-alpha gene expression, and body composition in elderly women. Journal of Aging Research, 2018.
