Cytokine-mediated changes associated with improvements in cancer-related fatigue induced by exercise: Results from a randomized pilot study of cancer patients receiving radiotherapy

Abstract

9632 Background: Radiation therapy (RTH) results in dysregulated inflammatory profiles which increase cancer-related fatigue (CRF). Research suggests physical exercise can have a positive influence on CRF during RTH. Exercise may mediate improvements in CRF through a self-regulating inflammatory exercise response involving cytokines and myokines (muscle contraction-induced cytokines known as exercise factors that mediate exercise benefits in other tissues) which help the body adapt to inflammation. We explored the influence of a home-based exercise intervention (HBEX), including resistance and aerobic training, on mediators of inflammation, as well as the association between changes in these mediators and CRF. Methods: Breast and prostate cancer patients (N=38; mean age=57; 71% breast/female), beginning at least 28 sessions of RTH, were randomized to a 4wk HBEX (7 days/wk) or standard care (SC; RTH with no exercise). Cytokines (IL-8, TNFα, TNFαr1, IL-8, IL-1β and IFNγ) and the myokine IL-6 were measured by enzyme-linked immunoassays and CRF was assessed via valid self-report questionnaires pre- and post-intervention. Results: ANCOVAs, controlling for baseline, revealed significant differences between groups in mean levels of IFNγ and IL-6 (p=<0.05) and a trend toward differences in IL-8 and TNFαr1 (p<0.10) with significant baseline interactions for IFNγ, IL-6 and IL-8 (p<0.05) post-intervention. ANCOVAs revealed no significant differences between groups in mean levels of TNFα and IL-1β. Pearson correlations revealed a significant inverse association between changes in IL-8 (p<0.05;r=-0.64) and CRF and a trend toward an inverse association between changes in IL-6 (p=0.10;r=-0.44) and CRF in the HBEX condition but not in the SC condition. Conclusions: These data suggest that exercise-induced changes in IL-8 and IL-6 may mediate improvements in CRF. Future phase III randomized controlled trials are needed with larger samples to fully investigate these relationships. Funded by NCI grant 1R25CA102618. No significant financial relationships to disclose.