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.

Circadian disruption: New clinical perspective of disease pathology and basis for chronotherapeutic intervention

“…Epidemiologic and clinical findings suggest too little daytime UV-B that leads to vitamin D deficiency/insufficiency and too much ALAN that leads to melatonin suppression are individually linked to enhanced risk for many of the same diseases and medical conditions. These so-called diseases of civilization include cancer, affective, metabolic, hypertensive, cardiac, vascular and immune system disorders (Arble et al, 2015;Cho et al, 2015;Cuesta et al, 2016;Johnston et al, 2016;Maury et al, 2014;Reitz & Martino, 2015;Smolensky et al, 2015a;Uth & Sleigh, 2014). Furthermore, ALAN contributes to, or at least reinforces, the eveningness chronotype of adolescence (Carskadon et al, 2004;Crowley et al, 2007;Roenneberg & Merrow, 2007;Vollmer et al, 2012) that may manifest as an extreme external desynchronization (relative to the phasing of normal environmental and societal cycles) of the sleep/ wake and other circadian rhythms.…”

“…ALAN is viewed today as a major threat to human health and well-being. Epidemiologic, clinical and laboratory animal investigations reveal evidence of increased risk for a broad array of medical conditions, including obesity; metabolic syndrome; diabetes; hypertension; cardiovascular disease; and breast, prostate, colorectal and other cancers (Arble et al, 2015;Cho et al, 2015;Cuesta et al, 2016;Haus & Smolensky, 2013;Johnston et al, 2016;Maury et al, 2014;Reitz & Martino, 2015;Rybnikova et al, 2016;Schernhammer et al, 2003;Smolensky et al, 2015a;Stevens & Zhu, 2015;Stevens et al, 2014;Uth & Sleigh, 2014;Van Cauter et al, 2008). The hypothesized mechanism is ALAN-induced alteration of the CTS, including the 24 h sleep/wake cycle.…”

Immunometabolism: Is it under the eye of the clock?

“…Therefore, circadian disruption, and not sleep loss leads to an increase in the innate immune response following experimentally induced jet-lag in mice [55], which has relevance for the increased inflammatory conditions observed with shift work. Stimulating night shift conditions disrupts the rhythm of immune function in humans [56]. Following night shift conditions the peak level of cytokines from peripheral blood mononuclear cells (PBMCs) treated with LPS was advanced by 4.5-6 hrs.…”

The Relationship Between Sleep Disorders and Quality of Life in Rotating Shift Workers at a Textile Factory

“…Night shifts result in lack of coordination in body's internal circadian rhythm with environmental factors regulating the body's biologic clock such as light-dark cycle, and this leads to disruption of normal physiological activity and psychological difficulties (14,15). Changing shift work from day to evening and night causes a person to regulate his/her sleep-wake cycle in accordance with the job duties and not based on the natural rhythms and physiological body.…”