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

Rahman, Shadab A.; Castanon-Cervantes, Oscar; Scheer, Frank A.J.L.; Shea, Steven A.; Czeisler, Charles A.; Davidson, Alec J.; Lockley, Steven W.

doi:10.1016/j.bbi.2014.11.003

Cited by 64 publications

(47 citation statements)

References 52 publications

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“…More recently, these results were confirmed and extended showing that exposing mice to LPS at the end of their rest period or beginning of the active period resulted in a stronger cytokine response and NF-κB activation compared with LPS exposure starting during the active period or beginning of the rest period (Marpegan et al 2009;Gibbs et al 2012;Nguyen et al 2013;Spengler et al 2012). Similar results have been obtained in humans using the LPS challenge both in vivo injecting LPS to healthy volunteers (Alamili et al 2014) and in vitro exposing blood samples obtained at different times of the day from volunteers to LPS (Petrovsky et al 1998;Rahman et al 2015). The greatest response of the immune system in terms of cytokine release occurs during the rest and early active periods.…”

Section: There Is a Circadian Variation In Immune Functionsupporting

confidence: 72%

A circadian based inflammatory response – implications for respiratory disease and treatment

Comas

Gordon

Oliver

et al. 2017

Sleep Science Practice

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Circadian clocks regulate the daily timing of many of our physiological, metabolic and biochemical functions. The immune system also displays circadian oscillations in immune cell count, synthesis and cytokine release, clock gene expression in cells and organs of the immune system as well as clock-controlled genes that regulate immune function. Circadian disruption leads to dysregulation of immune responses and inflammation which can further disrupt circadian rhythms. The response of organisms to immune challenges, such as allergic reactions also vary depending on time of the day, which can lead to detrimental responses particularly during the rest and early active periods. This review evaluates what is currently known in terms of circadian biology of immune response and the cross-talk between circadian and immune system. We discuss the circadian pattern of three respiratory-related inflammatory diseases, chronic obstructive pulmonary disease, allergic rhinitis and asthma. Increasing our knowledge on circadian patterns of immune responses and developing chronotherapeutic studies in inflammatory diseases with strong circadian patterns will lead to preventive measures as well as improved therapies focussing on the circadian rhythms of symptoms and the daily variation of the patients' responses to medication.

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Section: There Is a Circadian Variation In Immune Functionsupporting

confidence: 72%

A circadian based inflammatory response – implications for respiratory disease and treatment

Comas

Gordon

Oliver

et al. 2017

Sleep Science Practice

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“…We note that roughly 100–200 genes in the fly nervous system are under circadian control, and that many of them, like Achl , have never been studied in detail. Given the importance of understanding the molecular mechanisms by which circadian clocks control immune function (Edgar et al, 2016; Fortier et al, 2011; Gibbs et al, 2012; Keller et al, 2009; Rahman et al, 2015; Scheiermann et al, 2013; Silver et al, 2012b), we propose the testable hypothesis that Achl acts as a direct link between the circadian clock and immune function. This hypothesis is supported by several observations: Achl has high-amplitude mRNA rhythms that are likely driven by the clock, and it encodes an RNA-binding protein that may in turn regulate expression of downstream circadian effectors, perhaps including upstream regulators of immune activation.…”

Section: Discussionmentioning

confidence: 99%

Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila

Terry

Fejér

et al. 2017

Brain, Behavior, and Immunity

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The circadian clock is a transcriptional/translational feedback loop that drives the rhythmic expression of downstream mRNAs. Termed “clock-controlled genes,” these molecular outputs of the circadian clock orchestrate cellular, metabolic, and behavioral rhythms. As part of our on-going work to characterize key upstream regulators of circadian mRNA expression, we have identified a novel clock-controlled gene in Drosophila melanogaster, Achilles (Achl), which is rhythmic at the mRNA level in the brain and which represses expression of anti-microbial peptides in the immune system. Achilles knock-down in neurons dramatically elevates expression of crucial immune response genes, including IM1 (Immune induced molecule 1), Mtk (Metchnikowin), and Drs (Drosomysin). As a result, flies with knocked-down Achilles expression are resistant to bacterial challenges. Meanwhile, no significant change in core clock gene expression and locomotor activity is observed, suggesting that Achilles influences rhythmic mRNA outputs rather than directly regulating the core timekeeping mechanism. Notably, Achilles knock-down in the absence of immune challenge significantly diminishes the fly’s overall lifespan, indicating a behavioral or metabolic cost of constitutively activating this pathway. Together, our data demonstrate that (1) Achilles is a novel clock-controlled gene that (2) regulates the immune system, and (3) participates in signaling from neurons to immunological tissues.

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“…Daily patterns of immune factors and responses to immune challenge are modulated by sleep and circadian phase (Curtis et al, 2014; Fonken et al, 2013; Gibbs et al, 2012; Keller et al, 2009; Moller-Levet et al, 2013; Morrow and Opp, 2005; Narasimamurthy et al, 2012; Pollmacher et al, 1996; Rahman et al, 2014). Immune factors contribute to the natural sleep process (Imeri and Opp, 2009; Krueger et al, 2011; Marshall and Born, 2002) and sleep and circadian disruption are reported to alter inflammatory proteins (Axelsson et al, 2013; Chennaoui et al, 2011; Fondell et al, 2011; Frey et al, 2007; Haack et al, 2007; Meier-Ewert et al, 2004; Mullington et al, 2010; Redwine et al, 2000; Shearer et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance

Wright

Drake

Frey

et al. 2015

Brain, Behavior, and Immunity

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240

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Cortisol and inflammatory proteins are released into the blood in response to stressors and chronic elevations of blood cortisol and inflammatory proteins may contribute to ongoing disease processes and could be useful biomarkers of disease. How chronic circadian misalignment influences cortisol and inflammatory proteins, however, is largely unknown and this was the focus of the current study. Specifically, we examined the influence of weeks of chronic circadian misalignment on cortisol, stress ratings, and pro- and anti- inflammatory proteins in humans. We also compared the effects of acute total sleep deprivation and chronic circadian misalignment on cortisol levels. Healthy, drug free females and males (N=17) aged 20-41 participated. After three weeks of maintaining consistent sleep-wake schedules at home, six laboratory baseline days and nights, a 40-h constant routine (CR, total sleep deprivation) to examine circadian rhythms for melatonin and cortisol, participants were scheduled to a 25-day laboratory entrainment protocol that resulted in sleep and circadian disruption for eight of the participants. A second constant routine was conducted to reassess melatonin and cortisol rhythms on days 34-35. Plasma cortisol levels were also measured during sampling windows every week and trapezoidal area under the curve (AUC) was used to estimate 24-h cortisol levels. Inflammatory proteins were assessed at baseline and near the end of the entrainment protocol. Acute total sleep deprivation significantly increased cortisol levels (p<0.0001), whereas chronic circadian misalignment significantly reduced cortisol levels (p<0.05). Participants who exhibited normal circadian phase relationships with the wakefulness-sleep schedule showed little change in cortisol levels. Stress ratings increased during acute sleep deprivation (p<0.0001), whereas stress ratings remained low across weeks of study for both the misaligned and synchronized control group. Circadian misalignment significantly increased plasma tumor necrosis factor-alpha (TNF-α), interleukin 10 (IL-10) and C-reactive protein (CRP) (p<0.05). Little change was observed for the TNF-α/IL-10 ratio during circadian misalignment, whereas the TNF-α/IL-10 ratio and CRP levels decreased in the synchronized control group across weeks of circadian entrainment. The current findings demonstrate that total sleep deprivation and chronic circadian misalignment modulate cortisol levels and that chronic circadian misalignment increases plasma concentrations of pro- and antiinflammatory proteins.

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

Cited by 64 publications

References 52 publications

A circadian based inflammatory response – implications for respiratory disease and treatment

A circadian based inflammatory response – implications for respiratory disease and treatment

Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila

Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance

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