PMID- 24349251 OWN - NLM STAT- MEDLINE DCOM- 20141012 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 12 DP - 2013 TI - Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans. PG - e82291 LID - 10.1371/journal.pone.0082291 [doi] LID - e82291 AB - 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-alpha), interleukin (IL) -1beta, 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-alpha 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. FAU - Axelsson, John AU - Axelsson J AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden ; Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden ; Stress Research Institute, Stockholm University, Stockholm, Sweden. FAU - Rehman, Javaid-ur AU - Rehman JU AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Akerstedt, Torbjorn AU - Akerstedt T AD - Stress Research Institute, Stockholm University, Stockholm, Sweden. FAU - Ekman, Rolf AU - Ekman R AD - Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. FAU - Miller, Gregory E AU - Miller GE AD - Department of Psychology, University of British Columbia, Vancouver, Canada. FAU - Hoglund, Caroline Olgart AU - Hoglund CO AD - 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. FAU - Lekander, Mats AU - Lekander M AD - Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden ; Stress Research Institute, Stockholm University, Stockholm, Sweden ; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131211 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Chemokines) RN - 0 (Mitogens) RN - 0 (Phytohemagglutinins) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - Adult MH - Chemokines/*biosynthesis/*immunology MH - Humans MH - Hydrocortisone/metabolism MH - Leukocyte Count MH - Male MH - Mitogens/*immunology MH - Phytohemagglutinins/*immunology MH - Sleep Deprivation/*immunology MH - Th1 Cells/drug effects/*immunology MH - *Th1-Th2 Balance MH - Th2 Cells/drug effects/*immunology MH - Young Adult PMC - PMC3859577 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/12/19 06:00 MHDA- 2014/10/13 06:00 PMCR- 2013/12/11 CRDT- 2013/12/19 06:00 PHST- 2013/09/06 00:00 [received] PHST- 2013/10/31 00:00 [accepted] PHST- 2013/12/19 06:00 [entrez] PHST- 2013/12/19 06:00 [pubmed] PHST- 2014/10/13 06:00 [medline] PHST- 2013/12/11 00:00 [pmc-release] AID - PONE-D-13-37212 [pii] AID - 10.1371/journal.pone.0082291 [doi] PST - epublish SO - PLoS One. 2013 Dec 11;8(12):e82291. doi: 10.1371/journal.pone.0082291. eCollection 2013.