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      Systemic Elevation of Proinflammatory Interleukin-18 in Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) Coinfection Versus HIV or HCV Monoinfection

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          Summary

          HIV/hepatitis C virus coinfection and elevated IL-18 levels are both associated with inflammatory disease progression. IL-18 levels are significantly elevated in coinfected individuals, correlated inversely with CD4 count, and increased with incident HIV infection, potentially explaining enhanced inflammatory disease progression in coinfection.

          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.

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          Author and article information

          Journal
          Clin Infect Dis
          Clin. Infect. Dis
          cid
          Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
          Oxford University Press (US )
          1058-4838
          1537-6591
          01 March 2017
          09 February 2017
          01 March 2018
          : 64
          : 5
          : 589-596
          Affiliations
          [1 ] Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine ; and
          [2 ] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland
          Author notes

          Correspondence: A. L. Cox, Johns Hopkins University, Division of Infectious Diseases, Departments of Medicine and Oncology, 1503 E Jefferson St, Baltimore, MD 21231 ( acox@ 123456jhmi.edu ).

          Article
          PMC5850551 PMC5850551 5850551 ciw771
          10.1093/cid/ciw771
          5850551
          27927859
          48fcb844-9c5c-4396-906d-91b62dfd1a80
          © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
          History
          : 13 August 2016
          : 01 November 2016
          : 14 November 2016
          Page count
          Pages: 8
          Funding
          Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060
          Funded by: National Institute on Drug Abuse 10.13039/100000026
          Categories
          Major Article

          HIV,HCV,coinfection,inflammation,cytokines.
          HIV, HCV, coinfection, inflammation, cytokines.

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