title: Impact of exercise on pro inflammatory cytokine levels and epigenetic modulations of tumor-competitive lymphocytes in Non-Hodgkin-Lymphoma patients-randomized controlled trial.
abstract: BACKGROUND
  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.
authors.affiliation: Department for Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Zimmer
authors.forename: Freerk T
authors.initials: FT
authors.lastname: Baumann
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Alexander
authors.initials: A
authors.lastname: Schenk
authors.forename: Christine
authors.initials: C
authors.lastname: Koliamitra
authors.forename: Patrizia
authors.initials: P
authors.lastname: Jensen
authors.forename: Andreas
authors.initials: A
authors.lastname: Mierau
authors.forename: Thorben
authors.initials: T
authors.lastname: Hülsdünker
authors.forename: Nina
authors.initials: N
authors.lastname: Reinart
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Thomas
authors.initials: T
authors.lastname: Elter
mesh_terms: D000107:Acetylation; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015444:Exercise; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D016207:Cytokines; D006657:Histones; D018836:Inflammation Mediators
keywords: epigenetics; exercise; inflammation; lymphoma; nk-cell