title: Impaired counter-regulation of interleukin-1 by the soluble IL-1 receptor type II in patients with chronic liver disease.
abstract: 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.
authors.affiliation: Academic Teaching Hospital Hall in Tyrol, Austria.
authors.forename: Othmar
authors.initials: O
authors.lastname: Ludwiczek
authors.forename: Edouard
authors.initials: E
authors.lastname: Vannier
authors.forename: Alexander
authors.initials: A
authors.lastname: Moschen
authors.forename: Adriana
authors.initials: A
authors.lastname: Salazar-Montes
authors.forename: Ingo
authors.initials: I
authors.lastname: Borggraefe
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
authors.forename: Barbara
authors.initials: B
authors.lastname: Enrich
authors.forename: Arthur
authors.initials: A
authors.lastname: Kaser
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.forename: Charles
authors.initials: C
authors.lastname: Dinarello
authors.forename: Herbert
authors.initials: H
authors.lastname: Tilg
mesh_terms: 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
chemical_list: D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II