Up-regulation of interleukin 33 and soluble ST2 serum levels in liver failure.
BACKGROUND
IL-33, a member of the IL-1 family, induces the production of pro-inflammatory and Th2-associated cytokines and may also serve as an 'alarmin' similar to HMGB1. Soluble ST2 has been implicated as a decoy receptor, to attenuate Th2 inflammatory responses. The relevance of both molecules in hepatic failure is unknown.


METHODS
The trial was a prospective preliminary study in a university hospital surgical ICU; 11 patients with acute liver failure (ALF) and 12 patients with acute-on-chronic liver failure (ACLF), who were admitted to the ICU; 14 patients with chronic hepatic failure (CHF) awaiting liver transplantation; 13 healthy individuals served as controls. IL-33 and soluble ST2 concentrations were determined by enzyme linked immunosorbent assay (ELISA).


RESULTS
The concentration of IL-33 and soluble ST2 was significantly higher in ALF, ACLF, and CHF patients compared with the controls. Soluble ST2 serum concentration was significantly elevated in ALF and ACLF compared with CHF; moreover, soluble ST2 was significantly higher in CHF compared with healthy controls. IL-33 and soluble ST2 serum levels correlated significantly (r = 0.6117, P < 0.0001). Moreover, there was a correlation between IL-33 serum levels and alanine aminotransferase (ALT) activity in CHF, ALF, and ACLF patients (r = 0.4321, P = 0.0171).


CONCLUSIONS
Our data provide evidence for elevated levels of IL-33 and soluble ST2 in liver failure, which could a sign of immune hyperactivation, and/or a mechanism to down-regulate inflammation. Especially, soluble ST2 maybe useful to discern acute from chronic hepatic failure or to monitor the course and the severity of the disease.
Roth
Georg A
GA
Department of Anesthesiology, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria. georg.roth@meduniwien.ac.at
Zimmermann
Matthias
M
Lubsczyk
Barbara A
BA
Pilz
Johannes
J
Faybik
Peter
P
Hetz
Hubert
H
Hacker
Stefan
S
Mangold
Andreas
A
Bacher
Andreas
A
Krenn
Claus G
CG
Ankersmit
Hendrik Jan
HJ
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000276:immunology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood*; D017093:Liver Failure / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood*; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface; D000410:Alanine Transaminase