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.