Susceptibility Rhythm to E. coli Endotoxin and Bioassay.
Abstract
Light-synchronized periodicity analysis reveals a susceptibility rhythm in C mice to E. coli endotoxin. Susceptibility varies predictably and significantly along the 24-hour time scale. A dose of endotoxin which is compatible with survival of most animals when given during middle of daily dark period is highly lethal when it is given 8-12 hours earlier or later. LD50 also was determined for 2 samples from identical batch of endotoxin tested 12 h apart on separate groups of comparable C mice kept under conditions standardized for periodicity analysis: Differences in potency significant at 1% were seen at 2 dose levels common to both assays, the computed “potency ratio” being 3.22.
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Conversely, there are hints that owing to an overshooting proinflammatory cytokine response, the immediate defense of antigen is impaired during sleep, particularly during SWS.
“Conversely, there are hints that owing to an overshooting proinflammatory cytokine response, the immediate defense of antigen is impaired during sleep, particularly during SWS (508,627,693,779).”
From About Sleep's Role in Memory (2013) · cites this paper as [508]
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“Conversely, there are hints that owing to an overshooting proinflammatory cytokine response, the immediate defense of antigen is impaired during sleep, particularly during SWS (508, 627, 693, 779).”
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BackgroundPERIODICITY IN RESPONSE AND SUSCEPTIBILITY TO ENVIRONMENTAL STIMULI *
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“A pioneering contribution to this area was made by Halberg [34] who discovered a diurnal susceptibility pattern in mice challenged with bacterial endotoxin.”
BackgroundCircadian Coordination of Antimicrobial Responses
Tognini, P., Thaiss, C. A., Elinav, E., & Sassone‐Corsi, P. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.07.007 · Cited by 65 · see citing works
Why Lungs Keep Time: Circadian Rhythms and Lung Immunity
Nosal, C. R., Ehlers, A., & Haspel, J. A. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034602 · Cited by 65 · see citing works
“(100), who noted that the degree of inflammation elicited by endotoxin depended on when it was administered.”
BackgroundThe circadian protein BMAL1 in myeloid cells is a negative regulator of allergic asthma
Zasłona, Z., Case, S., Early, J. O., Lalor, S. J., McLoughlin, R. M., Curtis, A. M., & O'Neill, L. A. J. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00072.2017 · Cited by 64 · see citing works
“Single-cell suspensions from lung digests were prepared as described in detail elsewhere (19).”
BackgroundMethodCircadian Disruption and Consequences on Innate Immunity and Inflammatory Response
Jerigová, V. Š., Zeman, M., & Okuliarová, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213722 · Cited by 65 · see citing works
“An immune challenge given at the end of the rest period led to a mortality rate of 80%, whereas the same LPS dose given in the middle of the active period resulted in a mortality rate of only about 20% [47].”
BackgroundGuerrero‐Vargas, N. N., Salgado‐Delgado, R., Basualdo, M. D. C., García, J., Guzmán‐Ruiz, M. A., Carrero, J. C., Escobar, C., & Buijs, R. M. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.05.012 · Cited by 62 · see citing works
“Also previous studies suggested an involvement of the SCN in the immune response; an increase in mortality and cytokines production was reported after the administration of 20 mg/kg of LPS at the end of the rest phase (ZT11), while similar injections at the end of the active phase (ZT19) were less harmful (Halberg et…”
InfluentialAspects of Human Chronopathology
Smolensky, M. H. (1983) · Topics in environmental physiology and medicine · doi:10.1007/978-1-4613-9496-9_5 · Cited by 63 · see citing works
Circadian Rhythms and the Gastrointestinal Tract: Relationship to Metabolism and Gut Hormones
Martchenko, A., Martchenko, S. E., Biancolin, A. D., & Brubaker, P. L. (2020) · Endocrinology · doi:10.1210/endocr/bqaa167 · Cited by 61 · see citing works
Principles of Clinical Chronobiology
Haus, E. L., & Touitou, Y. (1992) · Springer eBooks · doi:10.1007/978-3-642-78734-8_2 · Cited by 61 · see citing works
Heipertz, E. L., Harper, J., Lopez, C. A., Fikrig, E., Hughes, M. E., & Walker, W. E. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701677 · Cited by 56 · see citing works
“It is worth noting that the diurnal changes reported in the LPS model were substantial (34, 35), whereas the diurnal changes we report in the CLP model are more subtle.”
BackgroundResultImmunometabolism: Is it under the eye of the clock?
Early, J. O., & Curtis, A. M. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.10.006 · Cited by 57 · see citing works
Circadian rhythm disruption in critically ill patients
Felten, M., Dame, C., Lachmann, G., Spies, C., Rubarth, K., Balzer, F., Kramer, A., & Witzenrath, M. (2023) · Acta Physiologica · doi:10.1111/apha.13962 · Cited by 56 · see citing works
Daily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells
Silver, A. C., Buckley, S. M., Hughes, M. E., Hastings, A. K., Nitabach, M. N., & Fikrig, E. (2018) · Heliyon · doi:10.1016/j.heliyon.2018.e00579 · Cited by 55 · see citing works
Yamamura, Y., Yano, I., Kudo, T., & Shibata, S. (2010) · Chronobiology International · doi:10.3109/07420521003769111 · Cited by 53 · see citing works
“LPS-induced mortality is higher when injected during late afternoon to early night in comparison with during late night to early morning (Halberg et al., 1960; Liu et al., 2006).”
BackgroundMicroglial ablation in rats disrupts the circadian system
Sominsky, L., Dangel, T., Malik, S., et al. (2020) · The FASEB Journal · doi:10.1096/fj.202001555rr · Cited by 52 · see citing works
Melatonin regulates the rhythmic migration of neutrophils in live zebrafish
Ren, D., Li, Y., Hu, B., Wang, H., & Hu, B. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12230 · Cited by 49 · see citing works
“In particular, previous studies indicated that the sensitivity and vulnerability of mice to acute inflammatory insult by pathogens or their products exhibit rhythmicity, peaking at nighttime [11–14], and many immune components including macrophage cells, natural killer (NK) cells, spleen, and lymph nodes were shown to…”
BackgroundEndotoxin Disrupts Circadian Rhythms in Macrophages via Reactive Oxygen Species
Wang, Y., Pati, P., Xu, Y., Chen, F., Stepp, D. W., Huo, Y., Rudic, R. D., & Fulton, D. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0155075 · Cited by 51 · see citing works
Papaioannou, V. E., Mebazaa, A., Plaud, B., & Legrand, M. M. (2014) · Intensive Care Medicine Experimental · doi:10.1186/2197-425x-2-18 · Cited by 49 · see citing works
“[17] Susceptibility of mice to Escherichia coli endotoxin-induced lethality Lethality varied significantly throughout the day, depending on the time when mice were challenged”
BackgroundBennardo, M., Alibhai, F. J., Tsimakouridze, E. V., Chinnappareddy, N., Podobed, P. S., Reitz, C. J., Pyle, W. G., Simpson, J. A., & Martino, T. A. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00200.2016 · Cited by 48 · see citing works
“pneumonia (15), Coxsackie B virus (14), or lipopolysaccharideinduced endotoxic shock (21, 32).”
BackgroundInfluence of host defense activation on sleep in humans
Pollmächer, T., Mullington, J. M., Korth, C., & Hinze‐Selch, D. (1995) · Advances in Neuroimmunology · doi:10.1016/0960-5428(95)00006-n · Cited by 48 · see citing works
Perturbation of the circadian clock and pathogenesis of NAFLD
Mukherji, A., Dachraoui, M., & Baumert, T. F. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154337 · Cited by 50 · see citing works
Knitting Up the Raveled Sleave of Care
Yang, G., Paschos, G. K., Curtis, A. M., Musiek, E. S., McLoughlin, S. C., & FitzGerald, G. A. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007225 · Cited by 45 · see citing works
“Mouse B cells, T cells, macrophages, and natural killer cells contain cell-autonomous clocks (50), and the lethality from injected LPS— which causes septic shock—is greatest when the challenge occurs during transition into the activity phase (51), correlating with an enhanced production of IL-6 and TNFa from macrophag…”
BackgroundThe significance of circadian rhythms and dysrhythmias in critical illness
McKenna, H., Reiss, I. K. M., & Martín, D. (2017) · Journal of the Intensive Care Society · doi:10.1177/1751143717692603 · Cited by 44 · see citing works
“The clinical manifestations of rheumatoid arthritis follow the pattern of interleukin-6 (IL-6) expression, peaking in the morning, while mortality rates following administration of endotoxin depend upon the time of exposure.(28) The amplitude of circadian variation (the difference between the peak and trough) itself a…”
BackgroundSeasonality of Primarily Childhood and Young Adult Infectious Diseases in the United States
Shah, A. P., Smolensky, M. H., Burau, K. D., Cech, I. M., & Lai, D. (2006) · Chronobiology International · doi:10.1080/07420520600920718 · Cited by 44 · see citing works
“…agents), or physical (loud noise) agents is a critical deterministic factor of the magnitude of effect, even making the difference between death vs. survival (Feigin et al., 1969, 1972; Halberg, 1969; Halberg and Stevens, 1958; Halberg et al., 1955a, 1955b, 1959, 1960; Haus and Halberg, 1959).”
BackgroundLeone, M. J., Marpegán, L., Duhart, J. M., & Golombek, D. A. (2012) · Chronobiology International · doi:10.3109/07420528.2012.682681 · Cited by 42 · see citing works
“Lipopolysaccharide (LPS) challenge has been used as an immune stimuli in several works as a pathologic (Halberg et al., 1960) or physiologic model, depending on dose (Mullington et al., 2000; Thomson & Sutherland, 2005).”
BackgroundMethodInfluentialModulation of mammalian circadian rhythms by tumor necrosis factor-α
Paladino, N., Fedele, M. L. M., Duhart, J. M., Marpegán, L., & Golombek, D. A. (2014) · Chronobiology International · doi:10.3109/07420528.2014.886588 · Cited by 41 · see citing works
“Tissues corresponding to SCN regions were carefully dissected, as described above, from mice under 12:12 LD conditions at ZT3, ZT7, ZT11, ZT15, ZT19 and ZT23.”
Temporal variations in the susceptibility of white rats to pentobarbital sodium and tremorine
Pauly, J. E., & Scheving, L. E. (1964) · International Journal of Neuropharmacology · doi:10.1016/0028-3908(64)90090-5 · Cited by 41 · see citing works
A wheel of time: the circadian clock, nuclear receptors, and physiology: Figure 1.Preprint
Yang, X. (2010) · Genes & Development · doi:10.1101/gad.1920710 · Cited by 41 · see citing works
“It has been known for 50 years that mice have diurnal variation in survival rate after endotoxin shock (Halberg et al. 1960).”
BackgroundPronounced Inflammatory Response to Endotoxaemia during Nighttime: A Randomised Cross-Over Trial
Alamili, M., Bendtzen, K., Lykkesfeldt, J., Rosenberg, J., & Gögenür, I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087413 · Cited by 39 · see citing works
“were the first to investigate the circadian variation in the inflammatory response due to endotoxaemia [8], demonstrating that it was higher during day compared with night in mice.”
Background
- Authors
- Halberg, F., Johnson, E. A., Brown, B. W., & Bittner, J. J.
- Venue
- Experimental Biology and Medicine
- Publisher
- Frontiers Media SA
- Published
- 1960-01-01
- Volume
- 103
- Issue
- 1
- Pages
- 142-144
- ISSN
- 0071-3384 (ISSN-L)
- 1535-3702
- 1535-3699
- OpenAlex
- W2321428190
- Cited by
- 280
- References
- 0
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 21 · 2023: 16 · 2022: 12 · 2021: 13 · 2020: 19 · 2019: 14 · 2018: 9 · 2017: 14 · 2016: 12 · 2015: 8 · 2014: 11 · 2013: 11 · 2012: 11
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- endotoxin, Escherichia coli, circadian rhythm, periodicity analysis, light synchronization, mice, LD50, dose-response relationship, time of administration
- MeSH terms
- Biological Assay, Endotoxins, Escherichia coli, Humans
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