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Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans.

Rahman SA, Castanon-Cervantes O, Scheer FA, Shea SA, Czeisler CA, Davidson AJ, Lockley SW - Brain Behav. Immun. (2014)

Bottom Line: Various aspects of immune response exhibit 24-h variations suggesting that infection susceptibility and treatment efficacy may vary by time of day.These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles.These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function.

View Article: PubMed Central - PubMed

Affiliation: Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Ave., Boston, MA 02115, United States; Division of Sleep and Circadian Disorders, Department of Neurology, Brigham and Women's Hospital, 221 Longwood Ave., Boston, MA 02115, United States; Division of Sleep Medicine, Department of Medicine, Harvard Medical School, 164 Longwood Ave., Boston, MA 02115, United States. Electronic address: sarahman@rics.bwh.harvard.edu.

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Study protocol to assess daily rhythms under baseline (standard sleep-wake schedules) conditions and endogenous circadian rhythmicity of innate immune response in humansThis is an example protocol for a participant with a bedtime of midnight. Participants were enrolled in a 7-day (n = 3; A) or 9-day (n = 10; B) inpatient protocol in an environment free of time cues. White bars indicate exposure to ambient room light (~90 lux) and gray bars indicate exposure to dim ambient light (<3 lux). Black bars show scheduled sleep episodes in darkness. The schedule consisted of a 3-day baseline including admission (ADM), with 8:16 h sleep:wake cycle (based on average sleep times in the 7 days prior to study entry) and four meals per 24-hours (filled circles); an initial 40 h (A) or 50 h and 10 min (B) constant routine under dim light, semi-recumbent constant posture, forced wakefulness, and hourly space isocaloric meals (filled circles), a 16 h light exposure day (gray hatched bar); followed by 8 h sleep and then discharge (A) or a second 29 h 50 min constant routine followed by an 8 h sleep episode and then discharge (D/C) (B). In the present study data were analyzed from the baseline and initial CR components only using blood samples collected at 4 h intervals shown by the red lines.
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Figure 1: Study protocol to assess daily rhythms under baseline (standard sleep-wake schedules) conditions and endogenous circadian rhythmicity of innate immune response in humansThis is an example protocol for a participant with a bedtime of midnight. Participants were enrolled in a 7-day (n = 3; A) or 9-day (n = 10; B) inpatient protocol in an environment free of time cues. White bars indicate exposure to ambient room light (~90 lux) and gray bars indicate exposure to dim ambient light (<3 lux). Black bars show scheduled sleep episodes in darkness. The schedule consisted of a 3-day baseline including admission (ADM), with 8:16 h sleep:wake cycle (based on average sleep times in the 7 days prior to study entry) and four meals per 24-hours (filled circles); an initial 40 h (A) or 50 h and 10 min (B) constant routine under dim light, semi-recumbent constant posture, forced wakefulness, and hourly space isocaloric meals (filled circles), a 16 h light exposure day (gray hatched bar); followed by 8 h sleep and then discharge (A) or a second 29 h 50 min constant routine followed by an 8 h sleep episode and then discharge (D/C) (B). In the present study data were analyzed from the baseline and initial CR components only using blood samples collected at 4 h intervals shown by the red lines.

Mentions: Participants were studied for 7 or 9 days in an environment free of time cues (no access to windows, clocks, watches, live television, radio, internet, telephones, and newspapers and continually supervised by staff trained not to reveal information about the time of day). We analyzed the first 5 days of the protocol, that were identical for both the 7- and 9-day studies. Both protocols consisted of a 3-day baseline (8 h:16 h sleep:wake cycle based on average sleep times in the 7 days prior to study entry). The baseline days were followed by a 40-h CR in the 7-day study and a 50-h and 10 min CR in the 9-day study (Figure 1). During the CR episodes, participants were asked to remain awake while supervised in constant dim light in a semirecumbent posture, with daily nutritional intake divided into hourly portions (150 mEq Na+/100 mEq K+ (± 20%) controlled nutrient, isocaloric [basal energy expenditure x 1.3] diet, 2000–2500 mL fluids/24 h) (Lockley et al., 2006).


Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans.

Rahman SA, Castanon-Cervantes O, Scheer FA, Shea SA, Czeisler CA, Davidson AJ, Lockley SW - Brain Behav. Immun. (2014)

Study protocol to assess daily rhythms under baseline (standard sleep-wake schedules) conditions and endogenous circadian rhythmicity of innate immune response in humansThis is an example protocol for a participant with a bedtime of midnight. Participants were enrolled in a 7-day (n = 3; A) or 9-day (n = 10; B) inpatient protocol in an environment free of time cues. White bars indicate exposure to ambient room light (~90 lux) and gray bars indicate exposure to dim ambient light (<3 lux). Black bars show scheduled sleep episodes in darkness. The schedule consisted of a 3-day baseline including admission (ADM), with 8:16 h sleep:wake cycle (based on average sleep times in the 7 days prior to study entry) and four meals per 24-hours (filled circles); an initial 40 h (A) or 50 h and 10 min (B) constant routine under dim light, semi-recumbent constant posture, forced wakefulness, and hourly space isocaloric meals (filled circles), a 16 h light exposure day (gray hatched bar); followed by 8 h sleep and then discharge (A) or a second 29 h 50 min constant routine followed by an 8 h sleep episode and then discharge (D/C) (B). In the present study data were analyzed from the baseline and initial CR components only using blood samples collected at 4 h intervals shown by the red lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430446&req=5

Figure 1: Study protocol to assess daily rhythms under baseline (standard sleep-wake schedules) conditions and endogenous circadian rhythmicity of innate immune response in humansThis is an example protocol for a participant with a bedtime of midnight. Participants were enrolled in a 7-day (n = 3; A) or 9-day (n = 10; B) inpatient protocol in an environment free of time cues. White bars indicate exposure to ambient room light (~90 lux) and gray bars indicate exposure to dim ambient light (<3 lux). Black bars show scheduled sleep episodes in darkness. The schedule consisted of a 3-day baseline including admission (ADM), with 8:16 h sleep:wake cycle (based on average sleep times in the 7 days prior to study entry) and four meals per 24-hours (filled circles); an initial 40 h (A) or 50 h and 10 min (B) constant routine under dim light, semi-recumbent constant posture, forced wakefulness, and hourly space isocaloric meals (filled circles), a 16 h light exposure day (gray hatched bar); followed by 8 h sleep and then discharge (A) or a second 29 h 50 min constant routine followed by an 8 h sleep episode and then discharge (D/C) (B). In the present study data were analyzed from the baseline and initial CR components only using blood samples collected at 4 h intervals shown by the red lines.
Mentions: Participants were studied for 7 or 9 days in an environment free of time cues (no access to windows, clocks, watches, live television, radio, internet, telephones, and newspapers and continually supervised by staff trained not to reveal information about the time of day). We analyzed the first 5 days of the protocol, that were identical for both the 7- and 9-day studies. Both protocols consisted of a 3-day baseline (8 h:16 h sleep:wake cycle based on average sleep times in the 7 days prior to study entry). The baseline days were followed by a 40-h CR in the 7-day study and a 50-h and 10 min CR in the 9-day study (Figure 1). During the CR episodes, participants were asked to remain awake while supervised in constant dim light in a semirecumbent posture, with daily nutritional intake divided into hourly portions (150 mEq Na+/100 mEq K+ (± 20%) controlled nutrient, isocaloric [basal energy expenditure x 1.3] diet, 2000–2500 mL fluids/24 h) (Lockley et al., 2006).

Bottom Line: Various aspects of immune response exhibit 24-h variations suggesting that infection susceptibility and treatment efficacy may vary by time of day.These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles.These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function.

View Article: PubMed Central - PubMed

Affiliation: Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Ave., Boston, MA 02115, United States; Division of Sleep and Circadian Disorders, Department of Neurology, Brigham and Women's Hospital, 221 Longwood Ave., Boston, MA 02115, United States; Division of Sleep Medicine, Department of Medicine, Harvard Medical School, 164 Longwood Ave., Boston, MA 02115, United States. Electronic address: sarahman@rics.bwh.harvard.edu.

Show MeSH
Related in: MedlinePlus