Systemic elevation of proinflammatory interleukin-18 in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection versus HIV or HCV monoinfection

Rebecca Terilli Veenhuis, Jacquie Astemborski, Michael Anand Chattergoon, Paige Greenwood, Marissa Jarosinski, Richard D Moore, Shruti Hemendra Mehta, Andrea Cox

Research output: Contribution to journalArticle

Abstract

Background. Human immunodeficiency virus (HIV)/hepatitis C virus (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. Methods. Serum samples from 559 subjects with HIV monoinfection, HCV monoinfection, HIV/HCV coinfection, or people who inject drugs with neither infection were tested for IL-18 by enzyme-linked immunosorbent assay 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. Results. IL-18 was significantly elevated in coinfected individuals vs both monoinfections (P < .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 cell count (P < .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 < .001), while HIV suppression was associated with normal IL-18 levels. Four additional analytes (IP-10, IL-12/23p40, IFN-γ, IL-15) were found to be elevated in HIV/HCV coinfection when compared to both monoinfections. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)589-596
Number of pages8
JournalClinical Infectious Diseases
Volume64
Issue number5
DOIs
StatePublished - 2017

Keywords

  • Coinfection
  • Cytokines
  • HCV
  • HIV
  • Inflammation

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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