title: High plasma interleukin-18 levels mark the acute phase of hepatitis C virus infection.
abstract: BACKGROUND
  Proinflammatory cytokines play a critical role in antiviral immune responses. Large-scale genome studies have found correlations between single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 18 promoter and spontaneous control of hepatitis C virus (HCV), suggesting a role in clearance.
  
  
  METHODS
  Plasma IL-18, IL-1β, IL-6, IL-8, IL-12, interferon-γ, tumor necrosis factor-α, alanine aminotransferase (ALT), and HCV RNA levels were assessed longitudinally in subjects with known dates of HCV acquisition and analyzed according to IL-18 SNPs and outcome, either spontaneous clearance (SC) (n = 13) or persistent infection (PI) (n = 25).
  
  
  RESULTS
  No significant change in plasma proinflammatory cytokine expression was observed with the exception of IL-18, which increased in every subject with initial detection of HCV RNA. In every SC subject, IL-18 returned to the preinfection baseline concomitant with HCV control. In PI subjects, IL-18 declined following the acute phase of infection but remained above the preinfection baseline throughout chronic infection and did not correlate with HCV RNA or ALT levels.
  
  
  CONCLUSIONS
  Plasma IL-18 was an early and the most reliably detected host response to HCV infection measured in blood. Reduced IL-18 production with transition to chronic infection without correlation with HCV RNA or ALT levels suggests modulation of the innate response with persistent infection.
authors: Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors: Michael A
authors: MA
authors: Chattergoon
authors: Jordana S
authors: JS
authors: Levine
authors: Rachel
authors: R
authors: Latanich
authors: William O
authors: WO
authors: Osburn
authors: David L
authors: DL
authors: Thomas
authors: Andrea L
authors: AL
authors: Cox
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005838:Genotype; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000097:blood* / Q000235:genetics; D008137:Longitudinal Studies; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D020382:Interleukin-18; D012367:RNA, Viral; D000410:Alanine Transaminase