Increased susceptibility to apoptosis in circulating lymphocytes of critically ill patients.
OBJECTIVE
Lymphocyte apoptosis may influence immune responsiveness in systemic inflammation. Therefore, we investigated whether early signs of apoptosis (i.e., annexin-V binding and cell shrinkage) in peripheral lymphocytes were different among patients with severe sepsis, critically ill, nonseptic patients after major surgery, and healthy individuals.


METHODS
Ten patients with severe sepsis and ten critically ill, nonseptic patients after major surgery admitted to a surgical intensive care unit in a university hospital were included in the study. In addition, ten healthy blood donors were included for comparison. We investigated early signs of apoptosis using flow cytometric measurement of annexin-V binding to the cell surface and cell shrinkage of peripheral lymphocytes.


RESULTS
The percentage of apoptotic lymphocytes determined as annexin-V positive and propidium iodide negative cells was increased in freshly prepared cells of patients with severe sepsis (11.4 +/- 0.5%) and critically ill, nonseptic patients after major surgery (18.5 +/- 2.0%) relative to healthy blood donors (4.4 +/- 0.5%) (P < 0.05). No significant difference between patients with severe sepsis and patients after major surgery were found. Annexin-V binding increased significantly after OKT-3 stimulation of lymphocytes in patients with severe sepsis (34.4 +/- 1.6%), patients after major surgery (33.8 +/- 3.4%), and healthy blood donors (21.1 +/- 2.8%). No significant difference among groups was detected following OKT-3 stimulation. Furthermore, freshly isolated peripheral lymphocytes of patients with severe sepsis and critically ill, nonseptic patients after major surgery revealed a significantly higher proportion of cell shrinkage than in healthy blood donors (55.0 +/- 2.2%, 21.5 +/- 2.4% vs 3.6 +/- 0.7%; P < 0.05).


CONCLUSIONS
Circulating lymphocytes of critically ill patients show a high degree of early signs of cellular apoptosis. This may contribute to hyporesponsiveness of immune cells in systemic inflammation.
Schroeder
S
S
Klinik und Poliklinik für Anästhesiologie und Spezielle Intensivmedizin, Rheinischen Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. schroed@mailer.meb.uni-bonn.de
Lindemann
C
C
Decker
D
D
Klaschik
S
S
Hering
R
R
Putensen
C
C
Hoeft
A
A
von Ruecker
A
A
Stüber
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D016638:Critical Illness; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged