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.
N1 - Publisher Copyright:
© The Author 2017.
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
C2 - 27927859
AN - SCOPUS:85018176715
SN - 1058-4838
VL - 64
SP - 589
EP - 596
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 5
ER -