Increased leukocyte oxidative metabolism in severe sepsis and septic shock correlates with organ dysfunction and mortality

Introduction

Sepsis is the leading cause of mortality in the ICU. Sepsis morbidity and mortality are increasing through the years. Infection control depends on adequate microbe recognition and satisfactory cell activation. Paradoxically it has been seen that in sepsis cell activation can be both good and harmful to the host.

Objectives

To evaluate neutrophil activation in the continuum of sepsis measuring cell surface receptors and oxidative metabolism; to evaluate monocyte activation measuring oxidative metabolism; and to evaluate the correlation between cell activation and organ dysfunction.

Methods

Regarding the 1992 ACCP/SCCM consensus, 41 patients were included: 14 with sepsis, 12 with severe sepsis and 15 with septic shock. Seventeen healthy volunteers were included as the control group. TLR2, TLR4, CD11b, CD11c and CD66b expression on the neutrophil surface using whole blood were measured using flow cytometry. Reactive oxygen species formation due to DCFH oxidation was also measured by flow cytometry. Organ dysfunction was characterized and measured using the SOFA score.

Results

Diminished TLR2 and TLR4 expression was observed in septic shock compared with healthy volunteers (P = 0.05 and P = 0.06, respectively). There were no differences found in CD11b and CD11c expression. CD66b expression was increased when comparing the whole group of patients and the control group (P = 0.01). The neutrophil oxidative burst was increased in the whole group of patients compared with the control group at baseline and under PMA, fMLP, LPS and S. aureus stimulation (P < 0.001 for all conditions tested). The monocyte oxidative metabolism was also significantly increased in the whole patient group compared with the control group in all conditions tested (P < 0.01). Neutrophil and monocyte oxidative metabolism due to PMA, LPS and S. aureus stimulation in severe sepsis were diminished compared with sepsis and septic shock. A strong correlation was observed between neutrophil and monocyte oxidative metabolism. The SOFA score discriminated patients between survivors and nonsurvivors (ROC curve was 0.78; P = 0.02). A positive correlation was observed between organ dysfunction and oxidative metabolism in neutrophils and monocytes considering severe sepsis and septic shock. However, despite an oxidative burst in sepsis as high as in septic shock, no organ dysfunction was found in sepsis.

Conclusion

Neutrophils and monocytes are activated in the continuum of sepsis considering reactive oxygen species formation. Nonetheless, in the onset of sepsis increased oxidative metabolism was probably involved in resolution of the infectious course, but in the late stages of sepsis it was associated with tissue damage and, consequently, organ dysfunction and death.