Table 1.

Summary of clinical studies showing sepsis-induced alterations in leukocyte mitochondrial function.

References	Sepsis definition and patient age	Sample analyzed	Time of sample collection after sepsis diagnosis	Major alterations in mitochondrial function (as compared to controls)
Adrie et al. (32)	Severe sepsis and septic shock (>18 years)	PBMC	- Within 72 h - Between 7th and 10th day	- Increased membrane depolarization - Increased cell death markers
Belikova et al. (33)	Severe sepsis and septic shock (>18 years)	PBMC	- Within 48 h of ICU admission	- Reduced ADP-stimulated state 3 respiration and increased basal oxygen consumption
Japiassu et al. (34)	Septic shock (>18 years)	PBMC	- Within 48 h	- Reduced ADP-stimulated state 3 respiration and ATP synthase activity
Garrabou et al. (35)	SIRS with infection (no septic shock)	PBMC	- Exact time point not mentioned	- Decreased activities of ETC complexes I, III, and IV - Unaltered mitochondrial mass
Sjovall et al. (36)	Severe sepsis and septic shock (>18 years)	PBMC	- Within 48 h - Days 3–4 - Days 6–7	- Basal respiration and ETC complex I, II, and IV activities increased over time up to day 7
Weiss et al. (37) (pediatric study)	Septic shock with organ failure (<18 years)	PBMC	- Within 48 h - Days 5–7	- Unaltered basal and ATP linked respiration on days 1–2 - Spare respiratory capacity (SRC) decreased on days 1–2 - SRC recovered over days 5–7
Cheng et al. (31)	LPS infusion in healthy volunteers Bacterial and fungal sepsis patients (>18 years)	PBMC and monocytes	- LPS infusion for 4 h - Within 24 h for septic patients	- Decreased oxygen consumption in all models - Both glycolytic capacity and mitochondrial function impaired in septic PBMCs - Impaired ability to respond to a second stimulus
Merz et al. (38)	Septic shock (> 18 years)	Monocytes	−24 and 48 h - At shock resolution	- ETC complex I, IV, and ATP synthase activities elevated - No difference in ATP content
Jang et al. (39)	Sepsis and septic shock (>18 years)	PBMC	- Within 24 h	- Decreased ATP-linked respiration and reduced uncoupled complex I activity, and no differences in ETC complex II and IV activities. - Decreased spare respiratory capacity
Kraft et al. (40)	Sepsis with evidence of organ injury (>18 years)	PBMC	- Days 1, 3, and 5	- Reduced mitochondrial DNA and mitochondrial biogenesis - Increased plasma D-loop indicating mitochondrial damage - Alterations normalized over a week with patients' recovery
Weiss et al. (41) (pediatric study)	Sepsis and septic shock (<18 years)	PBMC	- Days 1–2, 3–5 and 8–14	- Decreased spare respiratory capacity (SRC) and increased mitochondrial content on days 1–2 - SRC recovered over time as patients improved over 14 days. - Low SRC associated with residual organ injury at day 14.
Weiss et al. (42) (pediatric study)	Severe sepsis and septic shock (<18 years)	PBMC	- Within hours - Days 3–5 and 8–14	- Decreased mitochondrial respiration observed in those septic PBMCs which showed reduced LPS-induced TNF-α and HLA-DR expression.
Clere-Jehl et al. (43)	Septic shock (<18 years)	PBMC	- Within 12 hours of noradrenaline start	- Increased basal and maximal respiratory capacity - Lower ATP synthase activity