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.
['Zimmer|Philipp|P|', 'Baumann|Freerk T|FT|', 'Bloch|Wilhelm|W|', 'Schenk|Alexander|A|', 'Koliamitra|Christine|C|', 'Jensen|Patrizia|P|', 'Mierau|Andreas|A|', 'Hülsdünker|Thorben|T|', 'Reinart|Nina|N|', 'Hallek|Michael|M|', 'Elter|Thomas|T|']
D000107:Acetylation D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D016022:Case-Control Studies D016207:Cytokines D044127:Epigenesis, Genetic D015444:Exercise D005260:Female D006657:Histones D006801:Humans D007150:Immunohistochemistry D018836:Inflammation Mediators D007694:Killer Cells, Natural D008228:Lymphoma, Non-Hodgkin D008297:Male D008875:Middle Aged D013601:T-Lymphocytes
exercise epigenetics nk-cell inflammation lymphoma