Abstract
Sepsis is associated with high rates of multiorgan failure and mortality. Altered mitochondrial function is an essential component of the early sepsis syndrome. However, its progression over time in peripheral blood mononuclear cells (PBMCs) is thus far unclear. Our purpose was to investigate this in the early phase of sepsis in ICU patients. A single-centre prospective observational cohort study was conducted in sepsis patients and compared with age- and sex-matched controls. Mitochondrial function was measured in PBMCs thrice during the first ICU week. RT-qPCR was used for semi-quantitative analysis of expression of genes involved in oxidative phosphorylation. Secondary endpoints included associations between mitochondrial function and (I) sepsis severity and (II) clinical outcomes, including 3-month mortality. Basal, ATP-linked, maximal and proton leak associated respiration were increased in sepsis patients (n = 25) compared to matched controls (n = 24) at all time points. This was associated with increased expression of SDBH (complex II) and ATP5F1A (complex V). Increased basal respiration was associated with 3-month mortality (HR 3.794, 95% CI 1.018–14.149, p = 0.047). No differences were observed in other secondary outcomes. PBMC mitochondria were shown to have an increased respiratory rate during the first week of sepsis. Moreover, a progressive increase was negatively associated with 3-month survival.
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The dataset supporting the conclusions of this article is available upon reasonable request from the corresponding author.
Abbreviations
- ADP:
-
Adenine diphosphate
- ATP:
-
Adenine triphosphate
- APACHE II:
-
Acute physiology and chronic health evaluation II
- BMI:
-
Body mass index
- CCCP:
-
Carbonyl cyanide m-chlorophenylhydrazone
- CI:
-
Confidence interval
- COPD:
-
Chronic obstructive pulmonary disease
- FEV1:
-
First second forced expiration
- FVC:
-
Forced vital capacity
- ICU:
-
Intensive care unit
- HR:
-
Hazard ratio
- IQR:
-
Interquartile range
- LMR:
-
Lymphocyte-monocyte ratio
- LOS:
-
Length of stay
- mNUTRIC:
-
Modified nutrition risk in critically ill score
- OXPHOS:
-
Oxidative phosphorylation system
- PBMC:
-
Peripheral blood mononuclear cells
- RCR:
-
Respiratory control ratio
- SARS-CoV-2:
-
Severe acute respiratory coronavirus 2
- SD:
-
Standard deviation
- SOFA:
-
Sequential organ failure assessment score
- TCA:
-
Tricarboxylic acid
- VIF:
-
Variation inflation factor
- WUR:
-
Wageningen University and Research
- ZGV:
-
Ziekenhuis Gelderse Vallei (Gelderse Vallei hospital)
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Acknowledgements
We owe thanks to the following people for their valuable contributions to data collection and the writing of preliminary reports: Monique Daanje, Rosan van den Boogaard, Demi Vogels, Laura Willemse, Marloes Snijder, Max van den Bergh, Julia Boeré, Susana Mittmann, Panagiotis Vlachogiannis, Marieke Krüger, Rebeka Darmati, Viditha Venkatramu and Lisa Kleverwal. We thank all participants of the study, as well as the MSc students and research nurses who aided in data collection.
Funding
This research was funded by the Research Foundation of the Intensive Care of Gelderse Vallei Hospital, Ede, The Netherlands. Any article processing charges will be put forth by Wageningen University & Research.
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HM and RSB contributed equally to data collection, data analysis and interpretation, and writing and revising of the manuscript. AvN, SG, and JdJ contributed to the conception of the study, data collection, analysis, interpretation, and revision of the manuscript. AW contributed to data collection and interpretation. AvZ contributed to the conception of the study, data interpretation and revision of the manuscript.
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Prof. Dr. Van Zanten reported receiving honoraria for advisory board meetings, lectures, research grants, and travel expenses from Abbott, AOP Pharma, Baxter, Danone-Nutricia, Dutch Medical Food, Fresenius Kabi, GE Healthcare, Medcaptain, Nestle, PAION and Rousselot. The other authors have nothing to declare.
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The study was approved by the Medical Ethical Committee of Wageningen University (METC-WUR, which was incorporated in the METC Oost-Nederland in 2021, dossier no. 2021–13011) and the assessment Committee for Scientific Research of ZGV (dossier no. 1801–004). The protocol was registered in the Netherlands Trial Register (number NTR6969) and was made available through the International Clinical Trial Registry Platform (NL5918). Patients were enrolled after signing the informed consent by the patient or legal representative.
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Moonen, H.P.F.X., Slingerland-Boot, R., de Jong, J.C.B.C. et al. Progression of peripheral blood mononuclear cell mitochondrial function during the early phase of sepsis in intensive care unit patients. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39202-2
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DOI: https://doi.org/10.1038/s41598-026-39202-2
