OXIDATIVE METABOLISM AND EXPRESSION OF CELL SURFACE RECEPTORS ON MONOCYTES AND NEUTROPHILS IN PATIENTS WITH SEPSIS, SEVERE SEPSIS AND SEPTIC SHOCK

Abstract

Leukocyte oxidative metabolism is of paramount importance in host defense against microorganisms, yet it may underlie tissue injury in sepsis. In this study we evaluated neutrophil and monocyte oxidative metabolism across the continuum of clinical sepsis, the expression of cell surface receptors, and the correlation between cell activation and organ dysfunction. Fortyone patients were included: 14 with sepsis (without organ dysfunction), 12 with severe sepsis and 15 with septic shock. Seventeen healthy volunteers (HV) were included as the control group. TLR2, TLR4, CD11b, CD11c and CD66b expression on neutrophil and monocyte surface were measured in whole blood using flow cytometry. Reactive oxygen species (ROS) generation was evaluated by DCFH oxidation. Organ dysfunction was assessed by SOFA score. TLR2 (p=0.05) and TLR4 (p=0.06) expression on neutrophils were decreased in septic shock, and CD66b expression was increased in severe sepsis (p=0.02) and septic shock (p=0.01) compared to HV. There were no differences in CD11b and CD11c expression. Neutrophil and monocyte ROS generation were increased in patients compared to the controls at baseline and after PMA, fMLP, LPS and S. aureus stimulation (p<0.001 for all conditions tested). A strong positive correlation was observed between neutrophil and monocyte oxidative metabolism. There were no correlations between TLRs expression and ROS generation. Organ dysfunction positively correlated with oxidative metabolism in neutrophils and monocytes in severe sepsis and septic shock. However, oxidative metabolism in sepsis was as high as in septic shock, denoting that during the onset of sepsis increased oxidative metabolism was probably involved in resolution of the infectious course, but on later stages of sepsis it was associated with tissue damage and consequently organ dysfunction and death.