In mammals, it is well documented that observable circadian rhythms are controlled by a central oscillator that is organized in transcriptional and translational feedback loops involving several clock genes. Although recent studies have demonstrated that clock genes oscillate in many peripheral tissues, their characteristics in the human immune system remain unknown. The present study investigates whether circadian clock genes function in human peripheral blood mononuclear cells. On the basis of studies derived from 3 human subjects under controlled conditions, circadian clock genes hPer1, hPer2, hPer3, and hDec1 are expressed in a circadian manner in human peripheral blood mononuclear cells (PBMCs), with the peak level occurring during the habitual time of activity.

In this combined field and laboratory investigation, the authors tested the efficacy of an intervention designed to promote circadian adaptation to night-shift work. Fifteen nurses working permanent night schedules (> or = 8 shifts/ 15 days) were recruited from area hospitals. Following avacation period of > or = 10 days on a regular daytime schedule, workers were admitted to the laboratory for the assessment of circadian phase via a 36-h constant routine. They returned to work approximately 12 night shifts on their regular schedules under one of two conditions. Treatment group workers (n = 10, mean age +/- SD = 41.7 +/- 8.8 years) received an intervention including 6 h of intermittent bright-light exposure in the workplace (approximately 3,243 lux) and shielding from bright morning outdoor light with tinted goggles (15% visual light transmission). Control group workers (n = 9, mean age +/- SD = 42.0 +/- 7.2 years) were observed in their habitual work environments. On work days, participants maintained regular sleep/wake schedules including a single 8-h sleep/darkness episode beginning 2 h after the end of the night shift. A second 36-h constant routine was performed following the series of night shifts. In the presence of the intervention, circadian rhythms of core body temperature and salivary melatonin cycles were delayed by an average (+/- SEM) of -9.32 +/- 1.06 h and -11.31 +/- 1.13 h, respectively. These were significantly greater than the phase delays of -4.09 +/- 1.94 h and -5.08 +/- 2.32 h displayed by the control group (p = 0.03 and p = 0.02, respectively). The phase angle between circadian markers and the shifted schedule was reestablished to its baseline position only in the treatment group of workers. These results support the efficacy of a practical intervention for promoting circadian adaptation to night-shift work under field conditions. They also underline the importance of controlling the overall pattern of exposure to light and darkness in circadian adaptation to shifted sleep/wake schedules.

This preliminary study is the first documentation of the effects of a shifted sleep/wake schedule on the circadian expression of both peripheral circadian oscillators in PBMCs and centrally-driven hormonal rhythms. In light of evidence associating clock gene expression with tissue function, the study of peripheral circadian oscillators has important implications for understanding medical disorders affecting night shift workers.

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The rhythmic expression of circadian clock genes in the neurons of the suprachiasmatic nucleus (SCN) underlies the manifestation of endogenous circadian rhythmicity in behavior and physiology. Recent evidence demonstrating rhythmic clock gene expression in non-SCN tissues suggests that functional clocks exist outside the central circadian pacemaker of the brain. In this investigation, the nature of an oscillator in peripheral blood mononuclear cells (PBMCs) is evaluated by assessing clock gene expression throughout both a typical sleep/wake cycle (LD) and during a constant routine (CR). Six healthy men and women aged (mean+/-SEM) 23.7+/-1.6 yrs participated in this five-day investigation in temporal isolation. Core body temperature and plasma melatonin concentration were measured as markers of the central circadian pacemaker. The expression of HPER1, HPER2, and HBMAL1 was quantified in PBMCs sampled throughout an uninterrupted 72 h period. The core body temperature minimum and the midpoint of melatonin concentration measured during the CR occurred 2:17+/-0:20 and 3:24 +/-0:09 h before habitual awakening, respectively, and were well aligned to the sleep/wake cycle. HPER1 and HPER2 expression in PBMCs demonstrated significant circadian rhythmicity that peaked early after wake-time and was comparable under LD and CR conditions. HBMAL1 expression was more variable, and peaked in the middle of the wake period under LD conditions and during the habitual sleep period under CR conditions. For the first time, bi-hourly sampling over three consecutive days is used to compare clock gene expression in a human peripheral oscillator under different sleep/wake conditions.

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The objective of this study was to quantify daytime sleep in night-shift workers with and without an intervention designed to recover the normal relationship between the endogenous circadian pacemaker and the sleep/wake cycle. Workers of the treatment group received intermittent exposure to full-spectrum bright light during night shifts and wore dark goggles during the morning commute home. All workers maintained stable 8-h daytime sleep/darkness schedules. The authors found that workers of the treatment group had daytime sleep episodes that lasted 7.1 ± .1 h (mean ± SEM) versus 6.6 ± .2 h for workers in the control group (p = .04). The increase in total sleep time co-occurred with a larger proportion of the melatonin secretory episode during daytime sleep in workers of the treatment group. The results of this study showed reestablishment of a phase angle that is comparable to that observed on a day-oriented schedule favors longer daytime sleep episodes in night-shift workers. (Author correspondence: diane.boivin@douglas.mcgill.ca ).

Work at unconventional hours can have both long and short term consequences. Shift workers are often required to perform their duties at times that are not favoured by the body's endogenous clock, or circadian pacemaker. A typical night shift worker, for example, may report reductions in alertness and performance during shifts, or significant difficulty attaining sleep of recuperative value in the day, all the while being more likely to develop health complications. The study of circadian physiology has significantly contributed to our current ability to aid the shift worker deal with atypical schedules. We discuss the usefulness of light treatment as a countermeasure for maladaptation to atypical work schedules.