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Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis*

Belikova, Ioulia PhD; Lukaszewicz, Anne Claire MD; Faivre, Valerie MS; Damoisel, Charles MD; Singer, Mervyn MD, FRCP; Payen, Didier MD, PhD

doi: 10.1097/01.CCM.0000295593.25106.C4
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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.

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

Setting: Critical care unit and laboratory, university hospital.

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

Interventions: 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.

Measurements and Main 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.

Conclusion: 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.

From the Department of Anesthesiology and Critical Care, Lariboisière University Hospital, Paris, France (IB, ACL, VF, CD, DP); and the Bloomsbury Institute of Intensive Care Medicine, Department of Medicine and Wolfson Institute of Biomedical Research, University College London, London, UK (MS).

Supported, in part, by the Université Paris 7 Denis Diderot, Ministère Français de l’Enseignement Supérieur et de la Recherche, plan quadriennal (équipe d’accueil EA 322) 2002–2006.

The authors have not disclosed any potential conflicts of interest.

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© 2007 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins