Soluble ST2 plasma concentrations predict mortality in severe sepsis.
OBJECTIVE
Patients with sepsis-after surviving the initial hyperinflammatory phase-display features consistent with immunosuppression, including hyporesponsiveness of immunocompetent cells to bacterial agents. Immunosuppression is thought to be facilitated by negative regulators of toll-like receptors, including membrane-bound ST2. We investigated the release of soluble ST2 (sST2), a decoy receptor that inhibits membrane-bound ST2 signaling, during sepsis.


METHODS
The study population comprised 95 patients with severe sepsis admitted to one of two intensive care units (ICUs) at the day the diagnosis of severe sepsis was made. Blood was obtained daily from admission (day 0) until day 7 and finally at day 14. Twenty-four healthy subjects served as controls. sST2 and cytokines were measured in serum.


RESULTS
Mortality among patients was 34% in the ICU and 45% in the hospital. On admission, sepsis patients had higher sST2 levels [10,989 (7,871-15,342) pg/ml, geometric mean (95% confidence interval, CI)] than controls [55 (20-145) pg/ml, P < 0.0001]. Serum sST2 remained elevated in patients from day 0 to 14 and correlated with disease severity scores (P < 0.001) and cytokine levels on day 0 and during course of disease (P < 0.0001). Nonsurvivors displayed elevated sST2 levels compared with survivors of the intensive care unit (P < 0.0001).


CONCLUSIONS
Sepsis results in sustained elevation of serum sST2 levels, which correlates with disease severity and mortality.
Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, The Netherlands. j.j.hoogerwerf@amc.uva.nl
Jacobien J
JJ
Hoogerwerf
Michael W T
MW
Tanck
Marieke A D
MA
van Zoelen
Xavier
X
Wittebole
Pierre-François
PF
Laterre
Tom
T
van der Poll
D018806:APACHE; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood* / Q000276:immunology; D018805:Sepsis / Q000097:blood* / Q000276:immunology / Q000401:mortality*
D016207:Cytokines; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface