Impact of exercise on pro inflammatory cytokine levels and epigenetic modulations of tumor-competitive lymphocytes in Non-Hodgkin-Lymphoma patients-randomized controlled trial.

Introduction Physical activity is associated with decreased cancer (recurrence) risk and a reduction in treatment-specific side effects. Exercise modulates cytokine expression and shows beneficial effects on cancer patients’ immune system. We investigated the following: (i) whether Non-Hodgkin-Lymphoma patients have increased serum macrophage migration inhibiting factor (MIF) and Interleukin-6 (IL-6) levels after immunochemotherapy; (ii) whether physical activity influences cytokine serum levels; and (iii) whether serum cytokine levels are associated with histone modifications in tumor-competitive immune cells. Methods Thirty patients and 10 healthy controls were randomised into an intervention and a control group. Participants of the intervention group exercised once for 30 min at moderate intensity on a bicycle ergometer. Blood samples were collected twice, before and after the intervention. MIF and IL-6 serum concentrations were detected by ELISA. Natural killer cells and CD8+ T-lymphocytes were isolated by magnetic labeled cell sorting. Isolated cells were stained and analyzed for global histone acetylation at histone 4, lysine 5 and histone three, lysine 9. Results Patients showed higher serum MIF and IL-6 baseline levels, and reduced NK-cell histone acetylation, indicating a reduced transcriptional activity of tumor-competitive lymphocytes. Changes in MIF correlated with altered NK-cell histone acetylation, leading to the hypothesis that MIF impacts NK-cells via epigenetic modifications. Further, the exercise intervention was associated with an increase in IL-6 and CD8+ T-lymphocyte histone acetylation. Conclusions We conclude that exercise induces changes in cytokine levels, thereby possibly affecting epigenetic patterns and activity of tumor-competitive lymphocytes.