title: Interleukin-1 receptor antagonist plasma concentration is specifically increased by alpha-2A-interferon treatment.
abstract: OBJECTIVE
  The mechanism of action of recombinant interferon-alpha (rIFN alpha) treatment in chronic hepatitis C is not fully understood, and may include modulation of the immune system as well as a direct antiviral effect. We have therefore evaluated the plasma concentrations of pro- and anti-inflammatory cytokines in patients with chronic hepatitis C before and during treatment with rIFN alpha.
  
  
  METHODS
  Twenty-three patients were studied. Plasma concentrations of IL-1 beta, IL-6, TNF, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptors (sTNFRs) type I and type II were determined twice before rIFN alpha treatment (on day -11 and day 1), and on days 11, 32 and 120 of treatment.
  
  
  RESULTS
  IL-1 beta, IL-6 and TNF plasma concentrations were rarely increased before treatment (in one, six and seven patients, respectively), and usually declined during treatment. sTNFRs I and II plasma concentrations were not increased either before or during treatment. This was not the case for IL-1RA. In untreated patients, the plasma concentration of IL-1RA was higher than normal in 16 out of 23 patients. When rIFN alpha treatment was initiated, there was a constant and dramatic increase in IL-1RA levels, which reached 8 times the upper limit of the normal range (p < 0.001 as compared to pretreatment values). This increase was sustained up to day 120.
  
  
  CONCLUSIONS
  These results indicate that induction of an anti-inflammatory status through modulation of the IL-1/IL-1RA balance may be a key mechanism of action of rIFN alpha treatment in chronic hepatitis C.
authors.affiliation: Service d'Hépato-Gastro-Entérologie, Hôpital A. Bèclère, Clamart, France.
authors.forename: S
authors.initials: S
authors.lastname: Naveau
authors.forename: D
authors.initials: D
authors.lastname: Emilie
authors.forename: E
authors.initials: E
authors.lastname: Borotto
authors.forename: A
authors.initials: A
authors.lastname: Portier
authors.forename: Y
authors.initials: Y
authors.lastname: Lazizi
authors.forename: V
authors.initials: V
authors.lastname: Giraud
authors.forename: L
authors.initials: L
authors.lastname: Grangeot-Keros
authors.forename: F
authors.initials: F
authors.lastname: Capron
authors.forename: P
authors.initials: P
authors.lastname: Galanaud
authors.forename: J C
authors.initials: JC
authors.lastname: Chaput
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D005260:Female; D006526:Hepatitis C / Q000097:blood* / Q000628:therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D011994:Recombinant Proteins; D012995:Solubility
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins