title: In humans IL-6 is released from the brain during and after exercise and paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice.
abstract: OBJECTIVE
  Plasma interleukin-6 (IL-6) increases during exercise by release from active muscles and during prolonged exercise also from the brain. The IL-6 release from muscles continues into recovery and we tested whether the brain also releases IL-6 in recovery from prolonged exercise in humans. Additionally, it was evaluated in mice whether brain release of IL-6 reflected enhanced IL-6 mRNA expression in the brain as modulated by brain glycogen levels.
  
  
  METHODS
  Nine healthy male subjects completed 4 h of ergometer rowing while the arterio-jugular venous difference (a-v diff) for IL-6 was determined. The IL-6 mRNA and the glycogen content were determined in mouse hippocampus, cerebellum and cortex before and after 2 h treadmill running (N = 8).
  
  
  RESULTS
  At rest, the IL-6 a-v diff was negligible but decreased to -2.2 ± 1.9 pg ml(-1) at the end of exercise and remained low (-2.1 ± 2.1 pg ml(-1) ) 1 h into the recovery (P < 0.05 vs. rest). IL-6 mRNA was expressed in the three parts of the brain with the lowest content in the hippocampus (P < 0.05) coupled to the highest glycogen content (3.2 ± 0.8 mmol kg(-1) ). Treadmill running increased the hippocampal IL-6 mRNA content 2-3-fold (P < 0.05), while the hippocampal glycogen content decreased to 2.6 ± 0.6 mmol kg(-1) (P < 0.05) with no significant changes in the two other parts of the brain.
  
  
  CONCLUSIONS
  Human brain releases IL-6 both during and in recovery from prolonged exercise and mouse data suggest that concurrent changes in IL-6 mRNA and glycogen levels make the hippocampus a likely source of the IL-6 release from the brain.
authors.affiliation: Department of Anesthesia, Department of Biology, University of Copenhagen, Copenhagen, Denmark. peter@prec.dk
authors.forename: P
authors.initials: P
authors.lastname: Rasmussen
authors.forename: J-C
authors.initials: JC
authors.lastname: Vedel
authors.forename: J
authors.initials: J
authors.lastname: Olesen
authors.forename: H
authors.initials: H
authors.lastname: Adser
authors.forename: M V
authors.initials: MV
authors.lastname: Pedersen
authors.forename: E
authors.initials: E
authors.lastname: Hart
authors.forename: N H
authors.initials: NH
authors.lastname: Secher
authors.forename: H
authors.initials: H
authors.lastname: Pilegaard
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D015444:Exercise / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012039:Regional Blood Flow; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D006003:Glycogen; D005947:Glucose