Heightened levels of circulating 20S proteasome in critically ill patients.
BACKGROUND
Recently, circulating proteasome core particles (20S proteasome) have been suggested as a marker of cell damage and immunological activity in autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte apoptosis with consecutive T-cell unresponsiveness is deemed to play a pivotal role in the sepsis syndrome. Moreover sepsis-induced muscle proteolysis mainly reflects ubiqutin proteasome-dependent protein degradation. We therefore sought to investigate serum levels of 20S proteasome in critical ill patients.


METHODS
Case-control-study at a university hospital intensive care unit; 15 patients recruited within 24-48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h of admission to the ICU, a control group of 15 patients who underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure the concentration of 20S proteasome in the sera of the patients and controls. Data are given as mean +/- SEM. Mann-Whitney U-test was used to calculate significance and a P-value of 0.05 was considered to be statistically significant.


RESULTS
Marked increase of 20S proteasome was detected in the sera of septic patients (33 551 +/- 10 034 ng mL-1) as well as in trauma patients (29 669 +/- 5750 ng mL-1). In contrast, significantly lower concentrations were found in the abdominal surgery group (4661 +/- 1767 ng mL-1) and in the healthy control population (2157 +/- 273 ng mL-1).


CONCLUSIONS
Detection of 20S proteasome may represent a novel marker of immunological activity and muscle degradation in sepsis and trauma patients, and may be useful in monitoring the clinical effect of proteasome-inhibitors.
Roth
G A
GA
Department of Surgery, Vienna Medical School, Vienna, Austria.
Moser
B
B
Krenn
C
C
Roth-Walter
F
F
Hetz
H
H
Richter
S
S
Brunner
M
M
Jensen-Jarolim
E
E
Wolner
E
E
Hoetzenecker
K
K
Boltz-Nitulescu
G
G
Ankersmit
H J
HJ
D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D016638:Critical Illness; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood*; D014947:Wounds and Injuries / Q000097:blood*
D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex