Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis.
OBJECTIVE
During sepsis, after an initial stimulation immune cells down-regulate their functions, leading to a state of immunosuppression. Because the mechanisms of such down-regulation are unclear, we investigated the hypothesis of an energetic failure of immune cells to participate in immune dysfunction.


METHODS
Cohort of septic shock patients to study peripheral blood mononuclear cells (PBMCs) biological energy in comparison to healthy volunteer cells.


METHODS
Critical care unit and laboratory, university hospital.


METHODS
Eighteen severe sepsis or septic shock patients and 32 healthy volunteers.


METHODS
Ex vivo measurement of oxygen consumption in PBMCs taken from patients. The PBMCs' mitochondrial oxidative phosphorylation was investigated using adenosine diphosphate stimulation. The plasma factors implication was tested, using healthy cells incubated in septic plasma, or septic cells incubated in healthy plasma, at different time points of sepsis. The relationship between monocyte human leukocyte antigen-DR expression and bioenergetic results was tested.


RESULTS
Baseline oxygen consumption was higher in septic PBMCs (p < .01), with an attenuated response to adenosine diphosphate stimulation (p < .01). Oxygen consumption of healthy PBMCs incubated in septic plasma mimicked the septic cell response, with amplitude depending on the duration of sepsis (days 0-28). Septic cells incubated in healthy plasma partially recovered normal patterns. Septic plasma incubation increased the fraction of decoupling oxygen consumption (p = .021). A relationship between oxygen consumption (baseline or adenosine diphosphate stimulated) and human leukocyte antigen-DR expression was observed for incubation with plasma sampled at different time points of septic shock.


CONCLUSIONS
Energetic failure of PBMCs in sepsis may be a factor associated with the modulation of immune response and human leukocyte antigen-DR phenotype, partially driven by plasma factors.
Belikova
Ioulia
I
Department of Anesthesiology and Critical Care, Lariboisière University Hospital, Paris, France.
Lukaszewicz
Anne Claire
AC
Faivre
Valerie
V
Damoisel
Charles
C
Singer
Mervyn
M
Payen
Didier
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation; D004734:Energy Metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption; D018805:Sepsis / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology
D006684:HLA-DR Antigens