Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Veenhuis RT

PROVIDER: S-EPMC5850551 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Veenhuis Rebecca T RT Astemborski Jacquie J Chattergoon Michael A MA Greenwood Paige P Jarosinski Marissa M Moore Richard D RD Mehta Shruti H SH Cox Andrea L AL

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20161207 5

<h4>Background</h4>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.<h4>Methods</h4>Serum fr ...[more]

PMID: 27927859

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Project description:Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS). Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be considered as preferential candidates.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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