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

Fingerprint

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

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 = "{Terilli Veenhuis}, Rebecca and Jacquie Astemborski and Chattergoon, {Michael Anand} and Paige Greenwood and Marissa Jarosinski and Moore, {Richard D} and Mehta, {Shruti Hemendra} and Andrea Cox",
year = "2017",
doi = "10.1093/cid/ciw771",
language = "English (US)",
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 - Terilli Veenhuis, Rebecca

AU - Astemborski, Jacquie

AU - Chattergoon, Michael Anand

AU - Greenwood, Paige

AU - Jarosinski, Marissa

AU - Moore, Richard D

AU - Mehta, Shruti Hemendra

AU - Cox, Andrea

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

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 5

ER -