Abstract
BackgroundInfection control depends on adequate microbe recognition and cell activation, yet inflammatory response may lead to organ dysfunction in sepsis. The aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction.MethodsA total of 41 patients were prospectively enrolled: 14 with sepsis, 12 with severe sepsis and 15 with septic shock. A total of 17 healthy volunteers were included as a control group. Patients were admitted to the Intensive Care Units and Emergency Rooms of Hospital Sao Paulo (Federal University of Sao Paulo) and Hospital Santa Marcelina, Sao Paulo, Brazil. Toll-like receptor (TLR)2, TLR4, CD11b, CD11c and CD66b expression on neutrophil surfaces and oxidative metabolism measured by non-fluorescent dichlorofluorescein (DCFH) oxidation in neutrophils and monocytes, using whole blood, were evaluated using flow cytometry. Organ dysfunction was measured using the sepsis-associated organ failure assessment (SOFA) score.ResultsTLR2 expression on neutrophils was found to be downregulated in septic shock patients compared to healthy volunteers (p = 0.05). No differences were found in CD11b and CD11c expression. CD66b expression was increased in the patient group compared to the control group (p = 0.01). Neutrophil and monocyte oxidative burst was increased in septic patients compared to the control group at baseline and after stimulation with phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS) and Staphylococcus aureus (p < 0.001 and p < 0.01, respectively, for neutrophils and monocytes in all tested conditions). A strong correlation was observed between neutrophil and monocyte oxidative metabolism. A SOFA score of 7 discriminated patients between survivors and non-survivors (area under the curve for reactive oxygen species (ROS) was 0.78; p = 0.02). ROS generation in patients with sepsis and septic shock with SOFA scores > 7 was higher than in patients with SOFA scores < 7, both in neutrophils and monocytes. However, oxidative burst in patients with sepsis was as high as in septic shock.ConclusionSurface receptors expression on neutrophils may be modulated across the continuum of sepsis, and enhanced or decreased expression may be found depending on the receptor considered. ROS generation is upregulated both in neutrophils and monocytes in septic patients, and it is differently modulated depending on the stage of the disease and the stimuli used.
Highlights
Severe sepsis and septic shock present with high incidence, morbidity and mortality, and are the most common causes of death in intensive care units [1]
Surface receptors expression on neutrophils may be modulated across the continuum of sepsis, and enhanced or decreased expression may be found depending on the receptor considered
Current data demonstrate that TLR2 and TLR4 are expressed on the cell surface of neutrophils from healthy volunteers and are upregulated after stimulation by LPS [11] or granulocyte-macrophage colony stimulating factor (GM-CSF) [12]
Summary
Severe sepsis and septic shock present with high incidence, morbidity and mortality, and are the most common causes of death in intensive care units [1]. AMP = antimicrobial peptide; DCFH-DA = 2',7'dichlorofluorescein diacetate; fMLP = formyl-methionyl-leucyl-phenylalanine; GM-CSF = granulocytemacrophage colony stimulating factor; GMFI = geometric mean fluorescence intensity; LPS = lipopolysaccharide; PAMPs = pathogen associated molecular pattern; PMA = phorbol myristate acetate; PRR = pattern recognition receptor; RNS = reactive nitrogen species; ROS = reactive oxygen species; RR = relative risk; SOFA = sepsis-associated organ failure assessment; TLR = toll-like receptor; TNFα = tumor necrosis factor alpha. Critical Care Vol 12 No 1 Martins et al. The pathogenesis of sepsis involves a complex interaction between host and infecting microorganism, including bacterial recognition, cell activation and transmigration, phagocytosis and destruction of the pathogen [3,4,5,6]. The aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction
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