title: Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans.
abstract: Various aspects of immune response exhibit 24-h variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-h variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48h of baseline conditions with standard sleep-wake schedules and 40-50h of constant environmental and behavioral (constant routine; CR) conditions. Significant 24-h rhythms were observed under baseline conditions in Monocyte Chemotactic Protein, Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 8 but not Tumor Necrosis Factor alpha whereas significant 24-h rhythms were observed in all four immune factors under CR conditions. The rhythm amplitudes, expressed as a percentage of mean, were comparable between immune factors and across conditions. In contrast, the acrophase time (time of the fitted peak) was different between immune factors, and included daytime and nighttime peaks and changes across behavioral conditions. 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.
authors.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.
authors.forename: Shadab A
authors.initials: SA
authors.lastname: Rahman
authors.affiliation: Neuroscience Institute, Morehouse School of Medicine, 720 Westview Dr. S.W., Atlanta, GA 30310, United States.
authors.forename: Oscar
authors.initials: O
authors.lastname: Castanon-Cervantes
authors.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.
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.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; Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97239, United States.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Shea
authors.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.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Czeisler
authors.affiliation: Neuroscience Institute, Morehouse School of Medicine, 720 Westview Dr. S.W., Atlanta, GA 30310, United States.
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Davidson
authors.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.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Lockley
mesh_terms: D000328:Adult; D018932:Chemokine CCL2 / Q000097:blood*; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D018932:Chemokine CCL2; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Chemokine; Circadian; Cytokine; Human; Immune response; Lipopolysaccharide; Melatonin; Sleep