title: Seven days' around the clock exhaustive physical exertion combined with energy depletion and sleep deprivation primes circulating leukocytes.
abstract: Both exhaustive physical exertion and starvation have been reported to induce depression of immune function. The aim of the present study was to investigate the inflammatory environment and state of activation and mediator-producing potential of circulating leukocytes during prolonged physical activity with concomitant energy and sleep deprivation. Eight well-trained males were studied during 7 days of semi-continuous physical activity. Sleep was restricted to about 1 h/24 h, energy intake to 1.5- 3.0 MJ/24 h. Blood was drawn at 07.00 A.M.: on days 0, 2, 4, and 7. Plasma levels of inflammation markers were measured. The response of circulating leukocytes to lipopolysaccharide (LPS; 1 microg mL(-1)), and the effect of added hydrocortisone (10 and 100 nmol L(-1)), were measured in the supernatant after 3 h of incubation in an ex vivo whole blood model. Activation of leukocytes steadily increased as measured by plasma matrix metalloproteinase-9, tumour necrosis factor-alpha, interleukin-1beta, and interleukin-6. Inhibitors of systemic inflammation were either unaltered (tissue inhibitor of matrix metalloproteinase-1) or elevated (plasma interleukin-1 receptor antagonist). Cortisol levels increased on days 2 and 4, but thereafter reverted to baseline values. The leukocytes responded to LPS activation with increasing release of inflammatory cytokines throughout the study period. The anti-inflammatory potency of hydrocortisone decreased. Prolonged multifactorial stress thus activated circulating immune cells and primed them for an increased response to a subsequent microbial challenge.
authors.affiliation: Division of Protection, Norwegian Defence Research Establishment, Forsvarets forskningsinstitutt/Avdeling B, N-2027, Kjeller, Norway. yngvar.gundersen@ffi.no
authors.forename: Yngvar
authors.initials: Y
authors.lastname: Gundersen
authors.forename: Per Kristian
authors.initials: PK
authors.lastname: Opstad
authors.forename: Trine
authors.initials: T
authors.lastname: Reistad
authors.forename: Ingjerd
authors.initials: I
authors.lastname: Thrane
authors.forename: Per
authors.initials: P
authors.lastname: Vaagenes
mesh_terms: D000328:Adult; D001835:Body Weight / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D005508:Food Deprivation / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D005082:Physical Exertion / Q000502:physiology*; D012795:Sialoglycoproteins / Q000097:blood; D012892:Sleep Deprivation / Q000097:blood / Q000503:physiopathology*; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D020738:Leptin; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9; D006854:Hydrocortisone