Impaired counter-regulation of interleukin-1 by the soluble IL-1 receptor type II in patients with chronic liver disease.
OBJECTIVE
To assess the production of the endogenous IL-1 modulators IL-1 receptor antagonist (IL-1Ra), type I and II soluble IL-1 receptors (IL-1sRI and II) in patients with chronic liver disease (CLD).


METHODS
Plasma levels of IL-1beta (IL-1beta) and IL-1 modulators were assessed in 126 CLD patients and 39 healthy controls. IL-1sRII was also measured in the supernatants of primary hepatocyte cultures.


RESULTS
Plasma IL-1sRI and IL-1Ra levels were significantly higher in cirrhotic CLD patients than in non-cirrhotic CLD patients and in controls. Levels did not depend on the etiology of CLD. Likewise, plasma IL-1beta levels were elevated in CLD patients compared with those in controls. In contrast, IL-1sRII levels did not differ between CLD patients and controls. Cultures of human primary hepatocytes showed that IL-1sRII is induced by IL-1beta, but not IL-6.


CONCLUSIONS
In cirrhotic CLD patients elevated plasma IL-1beta is not counteracted by endogenous levels of IL-1sRII, whereas high IL-1sRI is expected to neutralize the naturally occurring antagonist IL-1Ra, resulting in a dysregulation of the IL-1 system that might enhance pro-inflammatory activity of IL-1.
Ludwiczek
Othmar
O
Academic Teaching Hospital Hall in Tyrol, Austria.
Vannier
Edouard
E
Moschen
Alexander
A
Salazar-Montes
Adriana
A
Borggraefe
Ingo
I
Gabay
Cem
C
Enrich
Barbara
B
Kaser
Arthur
A
Siegmund
Britta
B
Dinarello
Charles
C
Tilg
Herbert
H
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053573:Receptors, Interleukin-1 Type I / Q000096:biosynthesis* / Q000097:blood; D053574:Receptors, Interleukin-1 Type II / Q000096:biosynthesis* / Q000097:blood
D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II