Does Combined Resistance and High-intensity Interval Training Counteract Inflammation Induced by Chemotherapy?

Fatigue is recognized as one of the most prevalent and burdensome adverse effects of cancer and its treatment, significantly impairing daily life activities with subsequent reductions in quality of life. Over the past decade, extensive research has shown that something as simple and accessible as exercise has the potential to counteract several cancer- and treatment-related adverse effects, including fatigue. The etiology of fatigue is assumed to be multifactorial, involving a variety of clinical, psychosocial, demographic, behavioral and biological elements such as systemic inflammation. Unraveling the mechanisms underlying the beneficial effects of exercise will provide a solid foundation for designing effective interventions to combat fatigue.

Our study, published in the March 2021 issue of Medicine & Science in Sports & Exercise_®, aimed to determine the role of inflammatory pathways in the association between exercise and fatigue in the randomized controlled OptiTrain study. In this study, we compared two different high-intensity exercise intervention regimens to usual care in patients undergoing adjuvant chemotherapy for primary breast cancer. Both exercise groups performed 3 × 3-minute bouts of high-intensity intermittent aerobic exercise. One was interspersed with lower-intensity aerobic exercise, whereas the other involved resistance exercise. Beneficial effects of exercise on fatigue were found in both exercise groups.

Blood samples were drawn before and after the intervention period, and a general increase in inflammation following adjuvant chemotherapy was seen in all groups. However, the increase in IL-6 and CD8a was less pronounced in participants who were randomized to the combined resistance and high-intensity interval group, with no attenuation in the participants randomized to the combined aerobic and high-intensity interval group. Why the response was specific to the combined resistance and high-intensity interval group has to be further investigated. However, it has been speculated that IL-6 is acutely released from skeletal muscle after exercise with sufficient load. This increased release can induce the anti-inflammatory cytokine IL-10 and subsequently reduce the expression of several pro-inflammatory markers from leukocytes, including IL-6. Our findings suggest that resistance exercises are an important component of an exercise program to reduce systemic inflammation.

Using pathway analyses, we identified IL-6 and CD8a as facilitating the exercise effects on fatigue, further supporting combined exercise interventions as a promising strategy to reduce chemotherapy-induced inflammation and subsequent fatigue. Knowledge about mechanisms underlying the beneficial effects of physical training will provide us with a solid basis for designing future exercise interventions. Ultimately, the development of individualized, targeted interventions to ameliorate fatigue offers good prospect to improve the long-term quality of life in the growing population of cancer patients.

About the authors:
Anouk Hiensch, M.Sc., is a Ph.D. candidate at the University Medical Center Utrecht in The Netherlands. Her research focuses on understanding the underlying mechanisms of the beneficial effects of exercise on fatigue in cancer survivors. Connect with Anouk at  A.*********@um********.nl .

Helene Rundqvist, Ph.D., is a senior researcher at the Karolinska Institutet in Stockholm, Sweden. Her research aims to identify the role of the immune system in mediating the effects of exercise interventions throughout the cancer continuum. Connect with Dr. Rundqvist at  he**************@ki.se .

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