Circadian Rhythm Disruption and Sepsis in Severe Trauma Patients

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Abstract

Background:

Circadian rhythms are important regulators of immune functions. Admission to an intensive care unit (ICU) may impact molecular clock activity and host response. Our objective was to assess and compare the immune circadian rhythms in trauma patients who develop and in those who do not develop sepsis.

Methods:

Blood samples were collected from severe trauma patients within 4 days after admission, with collections taking place every 4 hours over a 24-hours period. Cortisol and cytokines were measured with immunoassays. Whole-blood expression of three clock genes (Bmal1, Per2 and Per3) was studied by RT-qPCR. Neutrophils, monocytes and lymphocytes were analyzed by flow cytometry. Patients with and without sepsis were compared with the cosinor mixed model to estimate mesors, amplitudes, and acrophases.

Results:

Thirty-eight subjects were enrolled in the study, and 13 developed at least one septic episode. The septic patients had higher levels of cortisol than the non-septic patients (mesor at 489 nmol/L versus 405 nmol/L, p < 0.05) and delayed acrophases (22 h versus 15 h, p < 0.05). They also had lower lymphocyte counts (mesor at 785 versus 1,012 cells/μL, p < 0.05), higher neutrophil counts (mesor at 7,648 versus 7,001 cells/μL, p < 0.05), and monocyte counts (mesor at 579 versus 473 cells/μL, p < 0.05) than the non-septic patients. Although no amplitude difference was identified, the acrophases were significantly different between the two groups for lymphocytes, IL-10 and TNF.

Conclusion:

We demonstrated that all trauma patients had impaired circadian rhythms of cortisol, cytokines, leukocytes, and clock genes. Early circadian disruption was associated with the occurrence of sepsis and might be a marker of sepsis severity.

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