Background:  In the United States, 150,000 to 300,000 persons are infected with hepatitis C virus (HCV) and HIV. HIV co-infection is associated with reduced HCV treatment response rates, liver fibrosis, and more rapid HCV disease progression. Cytokines, as mediators of immune responses, inflammation, and fibrogenesis, may underlie differences in liver disease observed during HIV co-infection, permit HCV persistence, and likely influence treatment efficacy.

Methods:  We sought to determine the effects of viral infections on expression of the pro-inflammatory cytokines, interleukin 8 (IL-8) and tumor necrosis factor-a (TNF-a), and the fibrogenic cytokine, transforming growth factor (TGF-β); and to identify virologic and demographic variables associated with their expression. Samples from 242 participants in 4 infection groups (HCV⁺/HIV⁺, HCV⁺/HIV^–, HCV^–/HIV⁺, and HCV^–/HIV^–) were analyzed. Serum IL-8, TNF-a, and TGF-β were quantified using ELISA. Regression models were used to examine relationships between cytokine detection (IL-8 and TNF-a) or level (TGF-β) and the following variables:  infection status, age, gender, HCV and HIV RNA levels, HCV and HIV treatment histories, and HCV genotype.

Results:  IL-8 detection rates were highest in the HCV⁺/HIV⁺ (70%) and HCV⁺/HIV^– (91%) groups compared to HCV^–/HIV^– controls (30%; p < 0.0001), while TNF-a detection rates were < 30% in all groups. Median TGF-β levels were higher in HCV⁺/HIV⁺ compared with HCV⁺/HIV^– persons (4.56 vs 4.37 log₁₀ pg/mL; p < 0.0001). In univariate analysis, HIV co-infection was a significant predictor of decreased IL-8 detection but not of TNF-a detection. HCV RNA > 6 log₁₀ IU/mL and HIV co-infection were significantly associated with TGF-β.

Conclusions:  HIV co-infection significantly impacts the serum cytokine environment in HCV⁺ persons. Pro-inflammatory cytokines were not significantly up-regulated during HIV co-infection; however, HIV was associated with increased levels of TGF-β in HCV⁺ persons. Thus, HIV co-infection may further contribute to liver fibrosis during HCV infection by sustained induction of TGF-β expression. Prospective analyses should be conducted in HCV⁺/HIV^– and HCV⁺/HIV⁺ populations to determine relationships between cytokine expression and important indicators of liver disease such as histologic activity index, hepatic fibrosis, and HCV treatment response rates.

Keywords: Hepatitis C virus; cytokine; co-infection