Am. J. Respir. Crit. Care Med., Volume 164, Number 3, August 2001, 389-395

Mitochondrial Membrane Potential and Apoptosis Peripheral Blood Monocytes in Severe Human Sepsis

CHRISTOPHE ADRIE, MARIA BACHELET, MURIEL VAYSSIER-TAUSSAT, FRANÇOISE RUSSO-MARIE, ISABELLE BOUCHAERT, MINOU ADIB-CONQUY, JEAN-MARC CAVAILLON, MICHAEL R. PINSKY, JEAN-FRANÇOIS DHAINAUT, and BARBARA S. POLLA

Laboratory of Respiratory Physiology and Medical Intensive Care Unit, APHP, Cochin Port-Royal Hospital, INSERM U-^3 32, ICGM, and Immuno-Allergy Unit, Pasteur Institute, Paris, France; Division of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Reduced mitochondrial membrane potential (m), which is considered as an initial and irreversible step towards apoptosis, as well as cell death regulating proteins, such as Fas, Hsp70, or Bcl-2, may play an important role in sepsis. We studied the relationship between sepsis severity and peripheral blood monocyte m, cell death (necrosis and apoptosis), soluble Fas ligand, Hsp70, and Bcl-2 expression over time in 18 patients with sepsis, and compared these data with those of a group of 17 healthy control subjects. All measurements were performed within 3 d of the onset of severe sepsis (T1), then 7 to 10 d later (T2), and finally at hospital discharge (T3). m was expressed as the percent monocytes with altered m (%m). Patients with sepsis had greater %m at T1 and T2 but not at T3 (14.6 ± 2.6% and 15.9 ± 2%, respectively, versus control 6.6 ± 0.2%, p < 0.01). Septic patients exhibited greater cell death in their monocytes and had greater Hsp70 expression only at T1. Bcl-2 levels were similar in septic and control subjects. Comparing survivors with non-survivors of sepsis, nonsurvivors had a greater %m at T1 (26.4 ± 5.3% versus 10.1 ± 2.7%, p < 0.01) and a significant decrease in Bcl-2 expression, whereas no difference was found in Hsp70 levels. These results indicate that mitochondrial dysfunction and subsequent cell death occur in severe sepsis and suggest that %m is a marker of severity in human sepsis.

Keywords: mitochondria; apoptosis; sepsis; heat-shock protein 70; proto-oncogene protein c-Bcl-2

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