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.
Woitas
Rainer P
RP
Department of Internal Medicine I, University of Bonn, D-53105 Bonn, Germany. woitas@uni-bonn.de
Petersen
Uwe
U
Moshage
Dirk
D
Brackmann
Hans H
HH
Matz
Bertfried
B
Sauerbruch
Tilman
T
Spengler
Ulrich
U
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014766:Viremia / Q000276:immunology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12