Leukocyte activation in sepsis; correlations with disease state and mortality

Objective: The immune response in sepsis shows a bimodal pattern consisting of an early, frequently exaggerated inflammatory response followed by a st ate of hyporesponsiveness often referred to as the compensatory anti-inflam matory response syndrome (CARS). Insight into the disease state may be help ful in deciding whether to choose immune stimulatory or anti-inflammatory t herapy in these patients and may determine clinical outcome. We hypothesize d that poor outcome in patients with sepsis is related to the severity of C ARS, as reflected in the degree of leukocyte activation. Design: Prospectiv e study. Setting: Intensive and respiratory care unit at a university hospi tal. Patients: Twenty consecutive patients with sepsis and 20 healthy age-m atched volunteers. Interventions: None. Measurements and Results: Analysis of surface expression of HLA-DR, CD11 b, ICAM-1, CD66 b, CD63 and CD64 on n eutrophils and monocytes by flow cytometry and determination of plasma conc entrations of lactoferrin, interleukin 6 and neopterin by ELISA at the time of diagnosis. Patient data were related to those of controls; moreover pat ient data between survivors and non-survivors were compared. Increased expr ession of all markers, except HLA-DR, was observed on both neutrophils and monocytes from patients compared to healthy controls. HLA-DR expression on monocytes was significantly decreased in patients with sepsis (p < 0.01). E xpression of CD11 b and HLE on neutrophils, and ICAM-1 on monocytes, were l ower in patients who died compared to those who survived (p < 0.05). Conclu sion: In sepsis, both neutrophils and monocytes are activated compared to h ealthy controls. Poor prognosis is associated with a lower expression of ac tivation markers on monocytes and neutrophils, suggesting that poor outcome in these patients may be due to the compensatory anti-inflammatory respons e.