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 state of hyporesponsiveness often referred to as the compensatory anti-inflammatory response syndrome (CARS). Insight into the disease state may be helpful in deciding whether to choose immune stimulatory or anti-inflammatory therapy in these patients and may determine clinical outcome. We hypothesized that poor outcome in patients with sepsis is related to the severity of CARS, as reflected in the degree of leukocyte activation.


METHODS
Prospective study.


METHODS
Intensive and respiratory care unit at a university hospital.


METHODS
Twenty consecutive patients with sepsis and 20 healthy age-matched volunteers.


METHODS
None.


RESULTS
Analysis of surface expression of HLA-DR, CD11b, ICAM-1, CD66b, CD63 and CD64 on neutrophils and monocytes by flow cytometry and determination of plasma concentrations of lactoferrin, interleukin 6 and neopterin by ELISA at the time of diagnosis. Patient data were related to those of controls; moreover patient data between survivors and non-survivors were compared. Increased expression 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). Expression of CD11b and HLE on neutrophils, and ICAM-1 on monocytes, were lower in patients who died compared to those who survived (p < 0.05).


CONCLUSIONS
In sepsis, both neutrophils and monocytes are activated compared to healthy controls. Poor prognosis is associated with a lower expression of activation markers on monocytes and neutrophils, suggesting that poor outcome in these patients may be due to the compensatory anti-inflammatory response.
Muller Kobold
A C
AC
Department of Internal Medicine, University Hospital Groningen, The Netherlands. a.c.muller@path.azg.nl
Tulleken
J E
JE
Zijlstra
J G
JG
Sluiter
W
W
Hermans
J
J
Kallenberg
C G
CG
Tervaert
J W
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D018375:Neutrophil Activation; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology* / Q000401:mortality; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D018709:Statistics, Nonparametric; D015996:Survival Rate
D000954:Antigens, Surface; D015415:Biomarkers