TY - JOUR
T1 - High plasma interleukin-18 levels mark the acute phase of hepatitis C virus infection
AU - Chattergoon, Michael A.
AU - Levine, Jordana S.
AU - Latanich, Rachel
AU - Osburn, William O.
AU - Thomas, David L.
AU - Cox, Andrea L.
N1 - Funding Information:
Financial support. This work was supported by National Institutes of Health grants U19 AI09025, R0113324, and R01AI077757. Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jir642
DO - 10.1093/infdis/jir642
M3 - Article
C2 - 21984735
AN - SCOPUS:80155188540
SN - 0022-1899
VL - 204
SP - 1730
EP - 1740
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -