Mitochondrial function of immune cells in septic shock: A prospective observational cohort study.

Merz, Tobias; Pereira, Adriano J; Schürch, Roger; Schefold, Joerg C.; Jakob, Stephan; Takala, Jukka; Djafarzadeh, Siamak (2017). Mitochondrial function of immune cells in septic shock: A prospective observational cohort study. PLoS ONE, 12(6), e0178946. Public Library of Science 10.1371/journal.pone.0178946

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BACKGROUND Reduced cellular ATP synthesis due to impaired mitochondrial function of immune cells may be a factor influencing the immune response in septic shock. We investigate changes in mitochondrial function and bioenergetics of human monocytes and lymphocyte subsets. METHODS Thirty patients with septic shock were studied at ICU admission, after 24 and 48 hours, and after resolution of shock. Enzymatic activities of citrate synthase and mitochondrial complexes I, IV, and ATP synthase and ATP content of monocytes, T-cells and B-cells and pro-inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine plasma concentrations were compared to samples from 20 healthy volunteers. RESULTS Large variations in mitochondrial enzymatic activities of immune cells of septic patients were detected. In monocytes, maximum levels of citrate synthase activity in sepsis were significantly lower when compared to controls (p = 0.021). Maximum relative enzymatic activity (ratio relative to citrate synthase activity) of complex I (p<0.001), complex IV (p = 0.017) and ATP synthase (p<0.001) were significantly higher. In T-cells, maximum levels of citrate synthase (p = 0.583) and relative complex IV (p = 0.602) activity did not differ between patients and controls, whereas levels of relative complex I (p = 0.006) and ATP synthase (p = 0.032) were significantly higher in septic patients. In B-cells of patients, maximum levels of citrate synthase activity (p = 0.004) and relative complex I (p<0.001) were significantly higher, and mean levels of relative complex IV (p = 0.042) lower than the control values, whereas relative ATP synthase activity did not differ (p = 1.0). No significant difference in cellular ATP content was detected in any cell line (p = 0.142-0.519). No significant correlations between specific cytokines and parameters of mitochondrial enzymatic activities or ATP content were observed. CONCLUSIONS Significant changes of mitochondrial enzymatic activities occur in human peripheral blood immune cells in septic shock when compared to healthy controls. Assessed sub-types of immune cells showed differing patterns of regulation. Total ATP-content of human immune cells did not differ between patients in septic shock and healthy volunteers.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care

UniBE Contributor:

Merz, Tobias; Schefold, Joerg C.; Jakob, Stephan; Takala, Jukka and Djafarzadeh, Siamak

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Mirella Aeberhard

Date Deposited:

07 Jul 2017 10:54

Last Modified:

07 Jul 2017 10:54

Publisher DOI:

10.1371/journal.pone.0178946

PubMed ID:

28591158

BORIS DOI:

10.7892/boris.101314

URI:

https://boris.unibe.ch/id/eprint/101314

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