The DOI matches its Crossref record.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cited by
Sorted by citations
Items 201–280 of 280
Seasonal variations in endotoxin sensitivity.
Végh, P., & Kováts, T. (1967) · PubMed · Cited by 5
Microbial Modulation of Arousal
Toth, L. A. (1998) · CRC Press eBooks · doi:10.1201/9780849331510.ch37 · Cited by 5
CHRONOTOXICOLOGY AND CHRONOPHARMACOLOGY WITH EMPHASIS ON CARCINOSTATIC AGENTS
Scheving, L. E., Tsai, T. H., & Pauly, J. E. (1986) · Elsevier eBooks · doi:10.1016/b978-0-08-034135-4.50008-3 · Cited by 5
Time of Day-Dependent Responses to Cisplatin Treatment in a Male Mouse Model of Hepatoma
Akyel, Y. K., Selby, C. P., Sancar, A., & Abdo, A. N. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304251349893 · Cited by 4
“For example, the immune response to endotoxin exposure and the recovery from hepatectomy in rodents were found to vary depending upon the time of day of endotoxin exposure or hepatectomy (Halberg et al., 1960; S. Wei et al., 2022).”
Balit, N., Cermakian, N., & Khadra, A. (2024) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2024.111852 · Cited by 4
Circadian Control of Pulmonary Endothelial Signaling Occurs via the NADPH Oxidase 2-NLRP3 Pathway
Sengupta, S., Lee, Y., Tao, J. Q., Akolia, I., Louneva, N., Forrest, K. M., Paul, O., Brooks, T. G., Grant, G. R., Sehgal, A., et al. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304251363656 · Cited by 4
“…when studies showed that the mortality rate of mice exposed to the bacterial endotoxin (lipopolysaccharide, LPS) depended on the time of exposure (Halberg et al., 1960; Feigin et al., 1969, 1972; Shackelford and Feigin, 1973), that is, LPS challenge given at the end of the rest time resulted in…”
Daachi, F., Adi-Bessalem, S., Megdad-Lamraoui, A., & Laraba‐Djebari, F. (2025) · The Journal of venomous animals and toxins including tropical diseases · doi:10.1590/1678-9199-jvatitd-2024-0059 · Cited by 4
“In this context, previous studies have also shown daily variation in the acute-phase response due to endotoxemia [44, 45].”
Feeding Pattern, Circadian Rhythm, and Immune Function: What do we know about?
Estanislau, T. B., Kruger, K., Neto, J. C. R., Padilha, C. S., Gonçalves, D. C., Minuzzi, L. G., & Lira, F. S. (2022) · Current Pharmaceutical Design · doi:10.2174/1381612828666220729091451 · Cited by 5
Poulsen, R. C., & Dalbeth, N. (2024) · Gout Urate and Crystal Deposition Disease · doi:10.3390/gucdd2020011 · Cited by 4
“Circadian rhythms in immune function were first demonstrated experimentally in 1960, when it was shown that a dose of Escherichia coli endotoxin that was highly lethal to mice when administered at one time of day was well-tolerated if administered 8–12 h earlier [34].”
BackgroundMcEwen, B. S., & Karatsoreos, I. N. (2011) · Springer eBooks · doi:10.1007/978-3-642-22272-6_3 · Cited by 5
Essays on Chronomics Spawned by Transdisciplinary Chronobiology
Halberg, F., Cornélissen, G., Otsuka, K., et al. (2001) · Cited by 4
Self-citationImplications and Applications of Circadian Susceptibility Rhythms: Chronomics and Anesthesia
Franz Halberg, A., Cornélissen, G., & Othild Schwartzkopff, A. (2009) · doi:10.1002/9780470498392.ch10 · Cited by 5
Self-citationCambar, J., L'Azou, B., & Cal, J. C. (1992) · Springer eBooks · doi:10.1007/978-3-642-78734-8_9 · Cited by 4
Nassar, A. I., Abdelhamid, A. F., Ramsay, G., et al. (2022) · medRxiv · doi:10.1101/2022.12.11.22283321 · Cited by 4
Circadian metabolism in myeloid cells
Xu, Y., Wang, C., & Ho, P. (2025) · Life Metabolism · doi:10.1093/lifemeta/loaf018 · Cited by 3
Dysfunctional circadian-driven dynamics in gut microbiota and tumor microenvironment
Peng, T., Wan, Y., Sun, Y., Ren, Y., Shi, F., Lv, Y., Wen, X., Chen, Q., Yang, X., Xu, S., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2526716 · Cited by 4
Preliminary insights on the daily rhythm of CRP and IL-6 in athletic horses
Aragona, F., Rizzo, M., Arfuso, F., Arrigo, F., Fazio, F., Giudice, E., Faggio, C., Piccione, G. G., & Giannetto, C. (2025) · Journal of Equine Veterinary Science · doi:10.1016/j.jevs.2025.105702 · Cited by 3
Logic of the Temporal Compartmentalization of the Hepatic Metabolic Cycle
Zhu, B. (2022) · Physiology · doi:10.1152/physiol.00003.2022 · Cited by 4
Biological Clocks and Immune Function
Walker, W. H., Meléndez‐Fernández, O. H., Becker‐Krail, D. D., & Nelson, R. J. (2023) · Masterclass in neuroendocrinology · doi:10.1007/978-3-031-21358-8_11 · Cited by 3
Circadian Rhythms, Immune Regulation, and the Risk for Sepsis
Sengupta, S., Smith, D. F., & Koritala, B. S. C. (2024) · Clinics in Perinatology · doi:10.1016/j.clp.2024.10.012 · Cited by 3
Otsuka, K., Cornélissen, G., & Halberg, F. (2016) · Springer eBooks · doi:10.1007/978-4-431-54631-3_4 · Cited by 3
Self-citationRole of Astrocytes in the Immune-Circadian Signaling
Duhart, J. M., Marpegán, L., Leone, M. J., & Golombek, D. A. (2013) · Advances in Neuroimmune Biology · doi:10.3233/nib-130058 · Cited by 3
Burn trauma disrupts circadian rhythms in rat liver.
Rao, R., Yang, Q., Orman, M. A., Francois Berthiaume, B., Ierapetritou, M., & Androulakis, I. P. (2016) · Europe PMC (PubMed Central) · Cited by 3
Clock gene affect the noncanonical NF-κB pathway via circadian variation of Otud7b
Hou, W., Jiang, Z., Ying, J., Ding, L., Li, X., Qi, F., Yang, S., Cheng, S., Wang, Y., Liu, Y., et al. (2017) · Biological Rhythm Research · doi:10.1080/09291016.2017.1323422 · Cited by 3
Feldman, J. F. (1989) · Springer eBooks · doi:10.1007/978-1-4615-8061-4_7 · Cited by 3
Chikungunya Virus, Metabolism, and Circadian Rhythmicity Interplay in Phagocytic Cells
Alvarez-García, L., Sánchez‐García, F. J., Vázquez-Pichardo, M., & Moreno‐Altamirano, M. M. B. (2023) · Metabolites · doi:10.3390/metabo13111143 · Cited by 3
“The time of day and BMAL1 expression have been linked to the quality of the immune response against pathogens and their byproducts [81,82].”
BackgroundAging alters rhythms in immunity
Curtis, A. M., & Carroll, R. G. (2022) · Nature Immunology · doi:10.1038/s41590-021-01099-6 · Cited by 2
Characteristics of Sleep in Critically Ill Patients: Part II: Circadian Rhythm Disruption
Mélone, M.-A., & Gehlbach, B. K. (2022) · Springer eBooks · doi:10.1007/978-3-031-06447-0_2 · Cited by 2
Circadian Regulation of Sleep: From Genes to Circuits
Hameed, N. A., & Barber, A. F. (2024) · Springer eBooks · doi:10.1007/978-3-031-62723-1_14 · Cited by 3
Circadian metabolic adaptations to infections
Costantini, C., Brancorsini, S., Grignani, F., Romani, L. R., & Bellet, M. M. (2025) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2023.0473 · Cited by 4
“A prototypical example of circadian-driven immune response is represented by high-dose lipopolysaccharide (LPS) challenge in which an increased mortality is observed when LPS is administered in the evening compared to the morning [4].”
Light-dark cycle and the response of liver temperature to cold in the rat
Kikuchi, M., Chiba, M., & Yoshida, A. (1973) · International Journal of Biometeorology · doi:10.1007/bf01553644 · Cited by 2
Circadian Organization of the Immune Response
Cardinali, D. P., Esquifino, A. I., Maestroni, G. J. M., & Pandi-Perumal, S. R. (2007) · Springer eBooks · doi:10.1007/978-0-387-69146-6_3 · Cited by 2
Circadian Rhythms of the Mouse
Jilge, B., & Kunz, E. (2004) · Elsevier eBooks · doi:10.1016/b978-012336425-8/50073-x · Cited by 3
Circadian Rhythms in Immune Function
Adams, K. L., Castañón‐Cervantes, O., & Davidson, A. J. (2015) · Wiley eBooks · doi:10.1002/9781118467831.ch14 · Cited by 2
Diurnal changes in the reaction of the corneal epithelium to hydroquinone
Zhirnova, A. A. (1971) · Bulletin of Experimental Biology and Medicine · doi:10.1007/bf00783316 · Cited by 2
Senna, C. A., Fedele, M. L. M., Aiello, I., Hokama, G., Golombek, D. A., & Paladino, N. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304251378607 · Cited by 1
“…mice injected with LPS at the end of the day (ZT11, where ZT0 marks light onset and ZT12 light offset) exhibit a mortality rate of approximately 80%, whereas those injected in the middle of the night (ZT19) have a mortality rate of about 30% (Halberg et al., 1960; Marpegan et al., 2009).”
Pearson, G., Baca, B. A., Wang, J., Reis, P., Gottwals, S., Santos, N., Burke, E. C., Denaroso, G., Burnside, A., Akli, S., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117133 · Cited by 3
“3 14–21 Thus, circadian rhythms and immune function are linked.”
A temporal dialogue between the circadian clock and chronic inflammatory diseases
Chen, S., & Ray, D. W. (2026) · Disease Models & Mechanisms · doi:10.1242/dmm.052749 · Cited by 2
“Evidence for circadian regulation of immunity dates back to the 1950s, when Halberg and colleagues reported daily rhythms in circulating eosinophils and endotoxin susceptibility in mice (Halberg and Visscher, 1950; Halberg et al., 1960).”
Physiological and Psychological Effect of Light
Baldanzi, E. (2014) · Green energy and technology · doi:10.1007/978-1-4471-6633-7_15 · Cited by 1
Circadian Clocks and Immune Functions
Nobis, C. C., Kießling, S., Labrecque, N., & Cermakian, N. (2017) · Springer eBooks · doi:10.1007/978-81-322-3688-7_22 · Cited by 1
Overview and Understanding of Human Circadian Immunology
Padem, N., & Fishbein, A. B. (2019) · Springer eBooks · doi:10.1007/978-3-030-14738-9_4 · Cited by 1
Telemetry in Nonclinical Drug Safety Assessment Studies
Gad, S. C., & Gad, S. C. (2015) · CRC Press eBooks · doi:10.1201/b18705-17 · Cited by 1
(2007) · Springer eBooks · doi:10.1007/978-1-4020-4701-5_11 · Cited by 1
Şahin, Z., Kalkan, Ö. F., Aktaş, O., & Kalkan, A. (2023) · Akdeniz Medical Journal · doi:10.53394/akd.1110074 · Cited by 2
Otsuka, K., Cornélissen, G., & Franz Halberg, A. (2016) · Springer eBooks · doi:10.1007/978-4-431-54631-3_13 · Cited by 1
Self-citationDiurnal fluctuations in responses of mouse corneal epithelial cells to vinblastin
Semenova, N. F. (1975) · Bulletin of Experimental Biology and Medicine · doi:10.1007/bf00835190 · Cited by 1
Maples, R. W., Quinn, G. M., Srinivasan, T., Dende, C., Hooper, L. V., & Pfeiffer, J. K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.24.701519 · Cited by 1
Steuerung tagesperiodischer Empfindlichkeitsschwankungen für Außenfaktoren
Bünning, E. (1963) · Springer eBooks · doi:10.1007/978-3-642-49684-4_13
Changes in cell reactions to adrenalin at different times of day
Semenova, N. F. (1971) · Bulletin of Experimental Biology and Medicine · doi:10.1007/bf00810331
The effects of the light-dark cycle and its inversion on the susceptibility of mice to lead acetate
HAYASHI, O., Chiba, M., & Kikuchi, M. (1987) · International Journal of Biometeorology · doi:10.1007/bf02202929
“Significant susceptibility rhythms have been also found for harmful agents, such as audiogenic stimulation (Halbert et al., 1955), E. coli endotoxin (Halberg et al., 1960), ethanol, ouabain (Nelson and Halberg, 1973), potassium cyanide (Bafitis et al., 1978) and chemical carcinogens (Iverson et…”
BackgroundDiurnal variations in the response of intestinal and corneal epithelial cells of mice to colchicine
Semenova, N. F. (1974) · Bulletin of Experimental Biology and Medicine · doi:10.1007/bf00808719
Kallur, S. D. (2012) · OakTrust (Texas A&M University Libraries)
Researchsweet time": circadian characterization of galectin-1 null mice
Casiraghi, L. P., Croci, D. O., Poirier, F., et al. (2010)
Takiguchi, R. S. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.41.2019.tde-18022019-092835
“Temporal control of tumor growth in nocturnal mammals: impact of the circadian system”Preprint
Wagner, P. M., Prucca, C. G., Velazquez, F. N., Alderete, L. G. S., Caputto, B. L., & Guido, M. E. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.25.114652
“While the host's differential time-of-day responses to lethal infections and endotoxins were first demonstrated 19 almost 60 years ago [32], recent studies clarified that many aspects of immune functions are also under the 20”
BackgroundControl of Diurnal Fluctuations in Responsiveness to External Factors
Bünning, E. (1964) · Heidelberg science library · doi:10.1007/978-3-662-22511-0_13
Circadian Organization of the Immune Response
Esquifino, A. I., & Cardinali, D. P. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-384691-4.00006-7
Steuerung tagesperiodischer Empfindlichkeitsschwankungen für Außenfaktoren
Bünning, E. (1963) · Springer eBooks · doi:10.1007/978-3-662-00852-2_13
Control of Diurnal Fluctuations in Responsiveness to External Factors
Bünning, E. (1967) · Heidelberg science library · doi:10.1007/978-1-4757-1157-8_12
Méndez‐Ferrer, S. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.717955333.793575325
Walking on Air: An Empirical Proof-of-Concept
McEachron, D. L. (2012) · Synthesis lectures on biomedical engineering · doi:10.1007/978-3-031-01653-0_2
Owolabi, A. T. Y., Schneider, P., & Reece, S. E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.22.554271
Rythme circadien et inflammation
Ea, H., & Gauffenic, A. (2023) · Elsevier eBooks · doi:10.1016/b978-2-294-78249-7.00017-5
Bartman, C. M., & Prakash, Y. S. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/bk9781839167553-00160
Clock Proteins and Circadian Rhythms in Immunity
Curtis, A. M., & KNAPP, M. S. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/bk9781839167553-00270
Chronobiology and Implications for Pharmacology
Gorman, M. R. (2024) · Springer eBooks · doi:10.1007/978-3-030-73317-9_86-1
Chronobiology and Implications for Pharmacology
Gorman, M. R. (2024) · Springer eBooks · doi:10.1007/978-3-031-35529-5_86
Palluth, L., Takahashi, J. S., & Green, C. B. (2025) · Life Metabolism · doi:10.1093/lifemeta/loaf034 · Cited by 2
“Specifically, lethality is higher when LPS is administered during the rest phase and lower when administered during the active phase [96].”
Wei, N., Saghafi, S., Khan, E., & Diekman, C. O. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304251370409 · Cited by 1
“Franz Halberg, who coined the term circadian in 1959, showed that the survival rate of mice injected with the endotoxin E. Coli depends on the time of day that it is injected [17].”
Steuerung tagesperiodischer Schwankungen des Ansprechens auf Außenfaktoren
Bünning, E. (1977) · Springer eBooks · doi:10.1007/978-3-642-66645-2_12
Dynamic mechanisms of time-of-day-dependent adaptive immunity and vaccination responses
Weng, X., Ouyang, Q., & Wang, H. (2026) · Biophysical Journal · doi:10.1016/j.bpj.2026.01.041
Loss of daily phase relations identified by multiomic analyses in acute pancreatitis
Waddell, H., Zheng, X., Neyton, L. P. A., Stevenson, T. J., Bochkina, N., & Mole, D. J. (2026) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2026.102533
“This was substantiated experimentally in mice by Halberg et al., who reported that mice exposed to LPS in the active vs rest phase had a statistically significant difference in observed mortality [45,46].”
Circadian rhythm involvement in the host immune response
Diallo, A. B. (2020) · theses.fr (ABES) · doi:10.70675/d0ae13c6zedf6z402cz9fbfz469e58c326a0
Circadian rhythm and host response : new insights on the role of the body temperature rhythm
Coiffard, B. (2021) · theses.fr (ABES) · doi:10.70675/3b9112a2z4af1z4ccdz9bf9z29331b5c67c4
Feraoun, G. N. Y. (2022) · theses.fr (ABES) · doi:10.70675/e8e7fd4azd930z4307zad62z2c0404a8d331
Mélone, M.-A. (2024) · theses.fr (ABES) · doi:10.70675/443e8c4fz712bz4232za67czb9fe970a0eeb
Opposing Effects of the Circadian Timing on Acute and Chronic Phases of Sepsis
Lan, S., Lang, S., Sun, X., Tian, R., Gao, F., & Qin, X. (2026) · The FASEB Journal · doi:10.1096/fj.202504451rr · Cited by 1
“Given the profound impact of circadian rhythms on sepsis, there has been an increase in interdisciplinary research be-tween chronobiology and sepsis [33].”
Chronotherapy with immune checkpoint inhibitors: The knowns, the unknowns, and the contested
Gül, Z. M., Zeng, Q., Merkler, D., et al. (2026) · Cancer Cell · doi:10.1016/j.ccell.2026.08.010
Time-Dependent Psychotropic Drug Effects
Nagayama, H., Cornélissen, G., Pandi-Perumal, S. R., & Franz Halberg, A. (2006) · Springer eBooks · doi:10.1007/0-387-27682-3_7
Self-citationConsiderations Specific to Animal Test Models
Gad, S. C., & Chengelis, C. P. (1998) · Elsevier eBooks · doi:10.1016/b978-012272250-9/50012-5
Metadata
- 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 › Critical Care and Intensive Care Medicine › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review