Interleukin‐15 and high‐intensity exercise: relationship with inflammation, body composition and fitness in cancer survivors

Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth. These anti-oncogenic effects of exercise were associated with the exercise-mediated release of myokines such as interleukin (IL)-15. However, no study has quantified the acute IL-15 response in human cancer survivors, and whether physiological adaptations to exercise training (i.e. body composition and cardiorespiratory fitness) influence this response. In the present study breast, prostate and colorectal cancer survivors (n = 14) completed a single bout of high-intensity interval exercise (HIIE) [4×4 min at 85-95% heart rate (HR) peak, 3 min at 50-70% HR peak] before and after 7 months of three times weekly high-intensity interval training (HIIT) on a cycle ergometer. At each time point venous blood was sampled before and immediately after HIIE to assess the acute myokine (IL-15, IL-6, IL-10, IL-1ra) responses. Markers of inflammation, cardiorespiratory fitness and measures of body composition were obtained at baseline and 7 months. An acute bout of HIIE resulted in a significant increase in IL-15 concentrations (pre-intervention: 113%; P = 0.013, post-intervention: 102%; P = 0.005). Post-exercise IL-15 concentrations were associated with all other post-exercise myokine concentrations, lean mass (P = 0.031), visceral adipose tissue (P = 0.039) and absolute <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> </mml:msub> <mml:annotation>${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$</mml:annotation></mml:semantics> </mml:math> peak (P = 0.032). There was no significant effect of 7 months of HIIT on pre- or post-HIIE IL-15 concentrations (P > 0.05). This study demonstrates HIIE is a sufficient stimulus to increase circulating IL-15 and other myokines including IL-6, IL-10 and IL-1ra which may be clinically relevant in the anti-oncogenic effect of exercise and repetitive exposure to these effects may contribute to the positive relationship between exercise and cancer recurrence. KEY POINTS: Exercise has been demonstrated to reduce the risk of cancer recurrence. Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth, mediated by exercise-induced myokines (IL-6 and IL-15). High-intensity interval exercise significantly increased myokines associated with the anti-oncogenic effect of exercise and the magnitude of response was associated with lean mass, but training did not appear to influence this response. Given IL-15 has been implicated in the anti-oncogenic effect of exercise and is being explored as an immunotherapy agent, high-intensity interval exercise may improve outcomes for people living beyond cancer through IL-15-mediated pathways. Interventions that increase lean mass may also enhance this response.