Crosstalk between the circadian clock circuitry and the immune system
Open accessAbstract
Various features, components, and functions of the immune system present daily variations. Immunocompetent cell counts and cytokine levels present variations according to the time of day and the sleep-wake cycle. Moreover, different immune cell types, such as macrophages, natural killer cells, and lymphocytes, contain a circadian molecular clockwork. The biological clocks intrinsic to immune cells and lymphoid organs, together with inputs from the central pacemaker of the suprachiasmatic nuclei via humoral and neural pathways, regulate the function of cells of the immune system, including their response to signals and their effector functions. Consequences of this include, for example, the daily variation in the response to an immune challenge (e.g., bacterial endotoxin injection) and the circadian control of allergic reactions. The circadian-immune connection is bidirectional, because in addition to this circadian control of immune functions, immune challenges and immune mediators (e.g., cytokines) were shown to have strong effects on circadian rhythms at the molecular, cellular, and behavioral levels. This tight crosstalk between the circadian and immune systems has wide-ranging implications for disease, as shown by the higher incidence of cancer and the exacerbation of autoimmune symptoms upon circadian disruption.
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IL-1beta and TNFalpha show a circadian rhythm in human blood, with peak levels at midnight and trough levels in the early morning.
“IL-1b and TNFa show a circadian rhythm in human blood, with peak levels at midnight, when cortisol is the lowest, and trough levels in the early morning, as plasma cortisol surges.24”
From The Gut Microbiome and the Brain (2014) · cites this paper as [24]
Increases of inflammatory markers accompany the process of aging, a phenomenon termed inflammaging.
“Furthermore, increases of inflammatory markers accompany the process of aging, a phenomenon termed inflammaging (96, 197).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [96]
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References 256 · Cited by 279
Research works printed but not linked: 2
- Hertoghe T (2005). The “multiple hormone deficiency” theory of aging: is human senescence caused mainly by multiple hormone deficiencies? Ann N Y Acad Sci, 1057, 448– 65. 16399912
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- Authors
- Cermakian, N., Lange, T., Golombek, D., Sarkar, D., Nakao, A., Shibata, S., & Mazzoccoli, G.
- Affiliations
- Douglas Mental Health University Institute (CA)
- University of Lübeck (DE)
- National University of Quilmes (AR)
- Rutgers, The State University of New Jersey (US)
- Juntendo University (JP)
- Waseda University (JP)
- Casa Sollievo della Sofferenza (IT)
- Corresponding author
- Mazzoccoli, Gianluigi
- ORCID
- Venue
- Chronobiology International
- Publisher
- Informa UK Limited
- Published
- 2013-05-22
- Volume
- 30
- Issue
- 7
- Pages
- 870-888
- ISSN
- 0742-0528 (ISSN-L)
- 1525-6073
- PMC
- PMC7195843
- OpenAlex
- W2038322087
- Cited by
- 279
- References
- 256
- Citations by year
- 2026: 24 · 2025: 21 · 2024: 19 · 2023: 34 · 2022: 16 · 2021: 15 · 2020: 25 · 2019: 24 · 2018: 19 · 2017: 27 · 2016: 11 · 2015: 21 · 2014: 18 · 2013: 4 · 2012: 1
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Chronobiology International (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- Ministero della Salute (RC1203ME46)
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute on Alcohol Abuse and Alcoholism (R37 AA08757, R37AA008757, R01AA015718)
- National Heart, Lung, and Blood Institute (R01HL088041)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- circadian clock, immune system, suprachiasmatic nucleus, macrophages, natural killer cells, lymphocytes, cytokines, sleep-wake cycle, allergic reactions, lipopolysaccharide response, circadian rhythm disruption, cancer, autoimmune disease
- MeSH terms
- Aging, Animals, Circadian Rhythm, Humans, Immune System, Immunity, Innate, Killer Cells, Natural, Sleep, Suprachiasmatic Nucleus, Lymphocyte Subsets, Cytokines, Circadian Clocks
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