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Rebecca T. Veenhuis, Jacquie Astemborski, Michael A. Chattergoon, Paige Greenwood, Marissa Jarosinski, Richard D. Moore, Shruti H. Mehta, Andrea L. Cox, Systemic Elevation of Proinflammatory Interleukin-18 in Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) Coinfection Versus HIV or HCV Monoinfection, Clinical Infectious Diseases, Volume 64, Issue 5, 1 March 2017, Pages 589–596, https://doi.org/10.1093/cid/ciw771
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Abstract
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.
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.
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.
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.
