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. 2002 Jun;8(3):562-6.
doi: 10.3748/wjg.v8.i3.562.

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

Rainer P Woitas  1 , Uwe Petersen, Dirk Moshage, Hans H Brackmann, Bertfried Matz, Tilman Sauerbruch, Ulrich Spengler
Affiliations

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

Rainer P Woitas et al. World J Gastroenterol. 2002 Jun.

Abstract

Aim: 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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
Contour plots of cytokine expression in CD14+ cells. These contour plots show representative experiments for the detection of spontaneous expression (buffer control, left column) and HCV NS5b-induced expression (1 μg/mL, right column) of IL-1β (a), IL-10 (b), IL-12 (c) and TNF-((d) in peripheral blood CD14+ monocytes of patient # 23 with chronic hepatitis C at 12 hours of incubation.
Figure 2
Figure 2
Induction of cytokines by the HCV NS4 protein. The graph displays the fractions of IL-1β (a), IL-10 (b), IL-12 (c) and TNF-((d) producing monocytes 12 hours after stimulation with recombinant NS4 protein (1 μg/mL) for patients with chronic hepatitis C (filled squares), aviremic anti-HCV seropositives (upward triangles), and non-HCV related controls (downward triangles). Each dot represents the mean percentage of a single patient obtained from triplicate experiments. The horizontal bar gives the mean of each group.
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