@article{2ee9344d7aea4e3a9ff6b9234570de0f,
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 48. h of baseline conditions with standard sleep-wake schedules and 40-50. h 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.",
keywords = "Chemokine, Circadian, Cytokine, Human, Immune response, Lipopolysaccharide, Melatonin, Sleep",
author = "Rahman, {Shadab A.} and Oscar Castanon-Cervantes and Scheer, {Frank A.J.L.} and Shea, {Steven A.} and Czeisler, {Charles A.} and Davidson, {Alec J.} and Lockley, {Steven W.}",
note = "Funding Information: None of the authors or their family members have a consulting relationship with a sponsor of the research reported in this manuscript. Possible conflicts of interest for all authors are disclosed below. OCC, FAJLS, SAS and AJD have no conflicts of interest to disclose related to this work. SAR has received research funding from Government of Ontario/Pharmacia Canada Inc./Genesis Research Foundation/OBGYN Graduate Scholarship in Science and Technology at the University of Toronto, Faculty of Medicine and the Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award from Canadian Institutes of Health Research, Standard Life (Canada) Inc.; SAR holds a patent for Prevention of Circadian Rhythm Disruption by Using Optical Filters and Improving sleep performance in subject exposed to light at night; SAR owns equity in Circadian ZircLight, Inc.; SAR is a co-investigator on studies sponsored by Biological Illuminations, LLC; Vanda Pharmaceuticals Inc. CAC (Disclosures for past 12 months) CAC has received consulting fees from or served as a paid member of scientific advisory boards for: Bombardier, Inc.; Boston Red Sox; Boston Celtics; Cephalon, Inc. (acquired by Teva Pharmaceutical Industries Ltd. October 2011); Michael Jackson{\textquoteright}s mother and children; Koninklijke Philips Electronics, N.V.; Novartis; United Parcel Services (UPS); and Vanda Pharmaceuticals, Inc.; and Zeo Inc. CAC owns an equity interest in Apple; Lifetrac, Inc.; Microsoft; Somnus Therapeutics, Inc.; and Vanda Pharmaceuticals, Inc., and received royalties from McGraw Hill, Penguin Press/Houghton Mifflin Harcourt, and Philips Respironics, Inc. Dr. Czeisler has also received research support from Cephalon, National Football League Charities, ResMed and Philips Respironics. CAC has received lecture fees from APSS (Associated Professional Sleep Societies); Harvard School of Public Health; Japan Society for Occupational Health; University of Washington. The Harvard Medical School Division of Sleep Medicine (HMS/DSM), which CAC directs, has received unrestricted research and educational gifts and endowment funds from: Boehringer Ingelheim Pharmaceuticals, Inc., Cephalon, Inc., Gerald McGinnis, Jazz Pharmaceuticals, Merck & Co., Inc., Peter C. Farrell, Ph.D., ResMed, and Respironics, Inc. The HMS/DSM has received gifts from many outside organizations and individuals including: Committee for Interns and Residents, Gerald McGinnis, Jazz Pharmaceuticals, Jordan{\textquoteright}s Furniture, NeuroScience, Novartis Consumer Health, Purdue Pharma, ResMed Foundation, Safeway, Transcept Pharmaceuticals, United Healthcare, Vanda Pharmaceuticals, Inc., Weight Watchers International and YMCA of the USA. The HMS/DSM Sleep and Health Education Program has received Educational Grant funding from Cephalon, Inc., Takeda Pharmaceuticals, Sanofi-Aventis, Inc. and Sepracor, Inc. CAC is the incumbent of an endowed professorship provided to Harvard University by Cephalon, Inc. and holds a number of process patents in the field of sleep/circadian rhythms (e.g., photic resetting of the human circadian pacemaker). Since 1985, CAC has also served as an expert witness on various legal cases related to sleep and/or circadian rhythms. SWL has received consulting fees from Naturebright, Sound Oasis, Thomas Jefferson University and Wyle Integrated Science and Engineering (NASA); unrestricted lighting equipment gifts from Biological Illuminations LLC, Bionetics Corporation, and Philips Lighting; unrestricted monetary gift to support research from Swinburne University of Technology, Australia; fellowship gift from Optalert, Pty, Melbourne, Australia; SWL holds equity in iSLEEP, Pty, Melbourne, Australia; advance author payment and royalties from Oxford University Press and payment for editing a textbook section from Elsevier; honoraria and/or travel and accommodation support for invited seminars, conference presentations or teaching from 8th International Conference on Managing Fatigue; Harvard University; Lighting Science Group Corp; Ontario Association of Fire Chiefs; Rio Tinto; Woolcock Institute of Medical Research; Wyle Integrated Science and Engineering; SWL has received investigator-initiated research grants from Biological Illuminations LLC, Philips Lighting and Philips-Respironics Inc.; sponsor-initiated research contracts with Vanda Pharmaceuticals; SWL holds a process patent for the use of short-wavelength light for resetting the human circadian pacemaker and improving alertness and performance which is assigned to the Brigham and Women{\textquoteright}s Hospital per Hospital policy. No income has been received. SWL also served as a paid expert on behalf of four public bodies in arbitration hearings related to sleep, circadian rhythms and work hours. Funding Information: We thank Elizabeth B. Klerman M.D. Ph.D., Peter Dearborn, research staff, and research participants at the Division of Sleep Medicine, BWH; the technical, dietary, nursing and medical staff at the Center for Clinical Investigation at the Brigham and Women{\textquoteright}s Hospital, Jonathan Williams M.D. for medical supervision; Core Laboratory staff (BWH) for melatonin assays. This work was supported by the National Space Biomedical Research Institute : HPF01301 ; National Heart, Lung, and Blood Institute : 1RC2HL101340-01 ; National Institute for Neurological Disorders and Stroke : U54NS060659 ; Atlanta Clinical and Translational Science Institute Pilot grant supported in part by PHS Grants: UL1 RR025008 , KL2 RR025009 or TL1 RR025010 from the Clinical and Translational Science Award program. SAR, SWL and CAC were supported in part by the National Space Biomedical Research Institute through NASA NCC 9-58 . SAS is supported by NASA Grant NASANNX1 OAR 1 OG and NHLBI Grant K24-HL076446 . FAS was supported by NHLBI Grant R01 HL094806 . The project described was supported by Brigham and Women{\textquoteright}s Hospital General Clinical Research Center Grant M01 RR02635 . The project described was supported by Clinical Translational Science Award UL1RR025758 to Harvard University and Brigham and Women{\textquoteright}s Hospital from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2014 Elsevier Inc..",
year = "2015",
month = jul,
day = "1",
doi = "10.1016/j.bbi.2014.11.003",
language = "English (US)",
volume = "47",
pages = "4--13",
journal = "Brain, Behavior, and Immunity",
issn = "0889-1591",
publisher = "Academic Press Inc.",
}