Effects of Exercise on Inflammation in Patients Receiving Chemotherapy: A Nationwide NCORP Randomized Clinical Trial

PURPOSE. A growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines. METHODS. This is a secondary analysis of a randomized trial studying 6 weeks of moderate-intensity walking and resistance exercise during chemotherapy compared to chemotherapy alone. At pre- and post-intervention, patients provided blood to assess serum concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, and IFN-γ, and receptor sTNFR1. We investigated relationships between cytokines using the correlations between changes in cytokine concentrations from pre- to post-intervention. RESULTS. We obtained complete data from 293 patients (149 randomized to exercise). Exercise strengthened the correlation between concentration changes of IL-10 and IL-6 (r=0.44 in exercisers vs. 0.11 in controls; p=0.001). We observed the same pattern for IL-10:IL-1β and IL-10:sTNFR1. Exercise also induced an anti-inflammatory cytokine profile, per reductions in pro-inflammatory IFNγ (p=0.044) and perhaps IL-1β (p=0.099, trend-level significance). CONCLUSIONS. Our hypothesis-generating work suggests that regular exercise during 6 weeks of chemotherapy may cause certain cytokine concentrations to change collectively (not independently). This work enhances our understanding of relationships between cytokines and complements traditional analyses of cytokines in isolation. Future work should test for replication and relationships to patient outcomes.