HCV-specific cytokine induction in monocytes of patients with different outcomes of hepatitis C.

Objective: Cytokine release by macrophages critically determines the type of immune response to an antigen. Therefore, we studied hepatitis C virus (HCV)-specific induction of interleukins-1 beta, -10, -12 (IL-1 beta, IL-10, IL-12), and tumor necrosis factor-alpha (TNF-alpha) in monocytes.

Methods: Intracellular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C, 14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear cells with recombinant core, NS3, NS4, NS5a and NS5b proteins.

Results: Patients with HCV viremia revealed greater spontaneous expression of IL-1beta, TNF-alpha, and IL-10. Furthermore, greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups (P<0.05). In contrast, neither IL-12 nor TNF-alpha was induced preferentially.

Conclusions: In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction - not counterbalanced by antiviral type 1 cytokines. This may contribute to persistent viral replication.