title: Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans.
abstract: Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1β, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5-6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep-wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers.
authors.affiliation: Centre for Study and Treatment of Circadian Rhythms, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada; and Laboratory of Molecular Chronobiology, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Cuesta
authors.affiliation: Centre for Study and Treatment of Circadian Rhythms, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Boudreau
authors.affiliation: Laboratory of Molecular Chronobiology, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Dubeau-Laramée
authors.affiliation: Laboratory of Molecular Chronobiology, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada diane.boivin@douglas.mcgill.ca nicolas.cermakian@mcgill.ca.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cermakian
authors.affiliation: Centre for Study and Treatment of Circadian Rhythms, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada; and diane.boivin@douglas.mcgill.ca nicolas.cermakian@mcgill.ca.
authors.forename: Diane B
authors.initials: DB
authors.lastname: Boivin
mesh_terms: D002940:Circadian Rhythm / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines