Daily Changes in the Expression of Clock Genes in Sepsis and Their Relation with Sepsis Outcome and Urinary Excretion of 6-Sulfatoximelatonin.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
pubmed:
14
8
2019
medline:
22
6
2021
entrez:
13
8
2019
Statut:
ppublish
Résumé
Whereas the circadian system controls the daily production of melatonin and the daily activity of the immune system, increasing evidences support the association between circadian misalignment with the alterations in the immune response and melatonin rhythm during sepsis. The aim of this study was to analyze the daily changes in clock genes expression and the urinary excretion of 6-SM (6-sulfatoxymelatonin, the major melatonin metabolite), and their connection with the innate immune activity, oxidative status in blood, and clinical outcome during sepsis. Healthy volunteers, non-septic intensive care unit (ICU) patients, and septic ICU patients, were evaluated. The expression of bmal1, per2, clock, and cry1 genes was determined by polymerase chain reaction in blood; 6-SM was assessed in urine by ELISA; plasma cytokines IL-1β, IL-6, IL-8, TNFα, and IL-10 were determined by a multiplex array method, and lipid peroxidation (LPO) and protein oxidation (AOPP) by spectrophotometry. Hematological and biochemical data, and clinical scores of the patients, were also recorded. Clock gene rhythm was maintained in non-septic patients but blunted in septic ones, whereas the innate immune and the oxidative stress responses were significantly higher in the latter. 6-SM excretion was also more elevated in septic than in non-septic patients, and it correlated with the degree of the immune response and oxidative status. 6-SM also correlated with SOFA and procalcitonin in the patients. Proinflammatory cytokines, LPO, and AOPP were normalized in the patients once recovered from sepsis. Our data suggest a relationship between clock genes rhythm disruption, the immune response, and the oxidative status, with 6-SM acting as a compensatory response. ICU conditions are not a main clock disrupter because of the significant differences found in the responses of septic versus non-septic patients under the same ICU environment.
Sections du résumé
BACKGROUND
Whereas the circadian system controls the daily production of melatonin and the daily activity of the immune system, increasing evidences support the association between circadian misalignment with the alterations in the immune response and melatonin rhythm during sepsis. The aim of this study was to analyze the daily changes in clock genes expression and the urinary excretion of 6-SM (6-sulfatoxymelatonin, the major melatonin metabolite), and their connection with the innate immune activity, oxidative status in blood, and clinical outcome during sepsis.
METHODS
Healthy volunteers, non-septic intensive care unit (ICU) patients, and septic ICU patients, were evaluated. The expression of bmal1, per2, clock, and cry1 genes was determined by polymerase chain reaction in blood; 6-SM was assessed in urine by ELISA; plasma cytokines IL-1β, IL-6, IL-8, TNFα, and IL-10 were determined by a multiplex array method, and lipid peroxidation (LPO) and protein oxidation (AOPP) by spectrophotometry. Hematological and biochemical data, and clinical scores of the patients, were also recorded.
RESULTS
Clock gene rhythm was maintained in non-septic patients but blunted in septic ones, whereas the innate immune and the oxidative stress responses were significantly higher in the latter. 6-SM excretion was also more elevated in septic than in non-septic patients, and it correlated with the degree of the immune response and oxidative status. 6-SM also correlated with SOFA and procalcitonin in the patients. Proinflammatory cytokines, LPO, and AOPP were normalized in the patients once recovered from sepsis.
CONCLUSION
Our data suggest a relationship between clock genes rhythm disruption, the immune response, and the oxidative status, with 6-SM acting as a compensatory response. ICU conditions are not a main clock disrupter because of the significant differences found in the responses of septic versus non-septic patients under the same ICU environment.
Identifiants
pubmed: 31403491
doi: 10.1097/SHK.0000000000001433
pii: 00024382-202005000-00005
doi:
Substances chimiques
RNA, Messenger
0
6-sulfatoxymelatonin
2208-40-4
CLOCK Proteins
EC 2.3.1.48
CLOCK protein, human
EC 2.3.1.48
Melatonin
JL5DK93RCL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
550-559Références
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