Systemic Elevation of Proinflammatory Interleukin 18 in HIV/HCV Coinfection versus HIV or HCV Monoinfection

Background: HIV/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 from 559 subjects with HIV monoinfection, HCV monoinfection, HIV/HCV coinfection, or people who inject drugs with neither infection was tested for IL-18 by ELISA 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 versus both monoinfections (p<0.0001) 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 count (p<0.0001), 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<0.001), while HIV suppression was associated with normal IL-18 levels. Four additional analytes (IP-10, IL-12/23p40, IFNy, 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.