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

Rebecca T. Veenhuis, Jacquie Astemborski, Michael A. Chattergoon, Paige Greenwood, Marissa Jarosinski, Richard D. Moore, Shruti H. Mehta, Andrea L. 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

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Interleukin-18
Coinfection
Hepacivirus
HIV
Infection
Inflammasomes
Cytokines
Incidence
Serum
Virus Activation
Interleukin-15
Viremia
Kidney Diseases
Interleukin-12
CD4 Lymphocyte Count
Immunoassay
Cardiovascular Diseases
Enzyme-Linked Immunosorbent Assay
Inflammation
T-Lymphocytes

Keywords

  • Coinfection
  • Cytokines
  • HCV
  • HIV
  • Inflammation

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

@article{0e6941029e924f458b9522ddc79f8074,
title = "Systemic elevation of proinflammatory interleukin-18 in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection versus HIV or HCV monoinfection",
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.",
keywords = "Coinfection, Cytokines, HCV, HIV, Inflammation",
author = "Veenhuis, {Rebecca T.} and Jacquie Astemborski and Chattergoon, {Michael A.} and Paige Greenwood and Marissa Jarosinski and Moore, {Richard D.} and Mehta, {Shruti H.} and Cox, {Andrea L.}",
year = "2017",
doi = "10.1093/cid/ciw771",
volume = "64",
pages = "589--596",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "5",

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TY - JOUR

T1 - Systemic elevation of proinflammatory interleukin-18 in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection versus HIV or HCV monoinfection

AU - Veenhuis,Rebecca T.

AU - Astemborski,Jacquie

AU - Chattergoon,Michael A.

AU - Greenwood,Paige

AU - Jarosinski,Marissa

AU - Moore,Richard D.

AU - Mehta,Shruti H.

AU - Cox,Andrea L.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Coinfection

KW - Cytokines

KW - HCV

KW - HIV

KW - Inflammation

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U2 - 10.1093/cid/ciw771

DO - 10.1093/cid/ciw771

M3 - Article

VL - 64

SP - 589

EP - 596

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T2 - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 5

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