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Lachmann G, Ananthasubramaniam B, Wünsch VA, et al. Circadian rhythms in septic shock patients. Ann Intensive Care. 2021;11(1):64doi: 10.1186/s13613-021-00833-5.
Lachmann, G., Ananthasubramaniam, B., Wünsch, V. A., Scherfig, L. M., von Haefen, C., Knaak, C., Edel, A., Ehlen, L., Koller, B., Goldmann, A., Herzel, H., Kramer, A., & Spies, C. (2021). Circadian rhythms in septic shock patients. Annals of intensive care, 11(1), 64. https://doi.org/10.1186/s13613-021-00833-5
Lachmann, Gunnar, et al. "Circadian rhythms in septic shock patients." Annals of intensive care vol. 11,1 (2021): 64. doi: https://doi.org/10.1186/s13613-021-00833-5
Lachmann G, Ananthasubramaniam B, Wünsch VA, Scherfig LM, von Haefen C, Knaak C, Edel A, Ehlen L, Koller B, Goldmann A, Herzel H, Kramer A, Spies C. Circadian rhythms in septic shock patients. Ann Intensive Care. 2021 Apr 26;11(1):64. doi: 10.1186/s13613-021-00833-5. PMID: 33900485; PMCID: PMC8076360.
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Ann Intensive Care. 2021 Apr 26;11(1):64. doi: 10.1186/s13613-021-00833-5.

Circadian rhythms in septic shock patients.

Annals of intensive care

Gunnar Lachmann, Bharath Ananthasubramaniam, Viktor A Wünsch, Lara-Marie Scherfig, Clarissa von Haefen, Cornelia Knaak, Andreas Edel, Lukas Ehlen, Barbara Koller, Anton Goldmann, Hanspeter Herzel, Achim Kramer, Claudia Spies

Affiliations

  1. Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
  2. Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178, Berlin, Germany.
  3. Institute for Theoretical Biology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  4. Humboldt Universität zu Berlin, Unter den Linden 6, 10117, Berlin, Germany.
  5. Laboratory of Chronobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  6. Department for Neurology and Neurological Intensive Care Medicine, Asklepios Fachklinikum Brandenburg, Brandenburg an der Havel, Deutschland.
  7. Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. [email protected].

PMID: 33900485 PMCID: PMC8076360 DOI: 10.1186/s13613-021-00833-5

Abstract

BACKGROUND: Despite the intensive efforts to improve the diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock.

METHODS: This prospective pilot study was performed at the university hospital Charité-Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 h over a 24-h period to isolate CD14-positive monocytes and to measure the expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. A rhythmicity score S

RESULTS: 77% of the measured clock genes showed inconclusive rhythms, i.e., neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 ± 0.26) compared to the control group (12 healthy young men, 0.70 ± 0.18). In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls.

CONCLUSION: Molecular rhythms in immune cells of septic shock patients were substantially altered and decreased compared to healthy young men. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and down-regulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms. Trail registration Clinical trial registered with www.ClinicalTrials.gov (NCT02044575) on 24 January 2014.

Keywords: Circadian rhythm; Clock genes; Pathophysiology; Sepsis; Septic shock

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