title: Systemic Elevation of Proinflammatory Interleukin 18 in HIV/HCV Coinfection versus HIV or HCV Monoinfection.
abstract: HIV/HCV coinfection and elevated interleukin (IL)-18 levels are both associated with enhanced progression of hepatic inflammation and increased risk of diabetes, kidney disease, and cardiovascular disease. IL-18 is a proinflammatory cytokine made upon activation of the inflammasome, an innate sensing system. We assessed whether increased IL-18 could explain the increased incidence and progression of inflammatory conditions seen with HIV/HCV coinfection.
  
  
  
  Serum from 559 subjects with HIV monoinfection, HCV monoinfection, HIV/HCV coinfection, or people who inject drugs with neither infection was tested for IL-18 by ELISA and for 16 other analytes by electrochemiluminescence immunoassay. IL-18 levels were measured in 14 additional chronically HCV infected subjects who developed incident HIV infection to determine if IL-18 increases with coinfection.
  
  
  
  IL-18 was significantly elevated in coinfected individuals versus both monoinfections (p<0.0001) independent of age, sex, and race. IL-18 levels were significantly higher in HIV monoinfection than in HCV monoinfection. High IL-18 levels were correlated with detectable HIV viremia and inversely with CD4 count (p<0.0001), consistent with HIV activation of the inflammasome resulting in CD4 T cell depletion. Incident HIV infection of chronically HCV infected subjects resulted in increased IL-18 (p<0.001), while HIV suppression was associated with normal IL-18 levels. Four additional analytes (IP-10, IL-12/23p40, IFNy, IL-15) were found to be elevated in HIV/HCV coinfection when compared to both monoinfections.
  
  
  
  HIV/HCV coinfection results in significantly elevated serum IL-18. The elevated levels of this proinflammatory cytokine may explain the increased incidence and progression of inflammatory illnesses seen in coinfected individuals.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Rebecca T
authors.initials: RT
authors.lastname: Veenhuis
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Jacquie
authors.initials: J
authors.lastname: Astemborski
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Chattergoon
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Greenwood
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Marissa
authors.initials: M
authors.lastname: Jarosinski
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Moore
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cox
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D060085:Coinfection / Q000097:blood* / Q000453:epidemiology; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D006526:Hepatitis C / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D016207:Cytokines; C000589760:IL18 protein, human; D020382:Interleukin-18
keywords: HCV; HIV; coinfection; cytokines; inflammation