title: Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans.
abstract: BACKGROUND
  Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion.
  
  
  METHODS
  Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h) followed by 5 days with restricted sleep (03.00-07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed.
  
  
  RESULTS
  5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day.
  
  
  CONCLUSIONS
  5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden ; Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden ; Stress Research Institute, Stockholm University, Stockholm, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Axelsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Javaid-ur
authors.initials: JU
authors.lastname: Rehman
authors.affiliation: Stress Research Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Torbjorn
authors.initials: T
authors.lastname: Akerstedt
authors.affiliation: Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Ekman
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, Canada.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Miller
authors.affiliation: Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden ; Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Solna, Stockholm, Sweden ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden ; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Caroline Olgart
authors.initials: CO
authors.lastname: Höglund
authors.affiliation: Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden ; Stress Research Institute, Stockholm University, Stockholm, Sweden ; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lekander
mesh_terms: D000328:Adult; D018925:Chemokines / Q000096:biosynthesis* / Q000276:immunology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008934:Mitogens / Q000276:immunology*; D010835:Phytohemagglutinins / Q000276:immunology*; D012892:Sleep Deprivation / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D018925:Chemokines; D008934:Mitogens; D010835:Phytohemagglutinins; D006854:Hydrocortisone