Lack of evidence for the Th2 predominance in patients with chronic hepatitis C

A T helper (Th)1 to Th2 shift has been proposed to be a critical pathogenic determinant in chronic hepatitis C. Here, we evaluated mitogen-induced and hepatitis C virus (HCV) core antigen-induced cytokine production in 28 pat ients with biopsy-proven chronic hepatitis C. Flow cytometry demonstrated t hat after mitogenic stimulation the percentage of Th2 cells (IL-4 + or IL-1 3 +) and Th0 cells (IFN-gamma /IL-4 + or IL-2/IL-13 +) did not differ betwe en patients and controls. In contrast, the percentage of Th1 cells (IFN-gam ma + or IL-2 +) was significantly increased in CD4 + , CD8 + , 'naive'-CD45 RA + and 'memory'-CD45RO + T-cell subsets from patients versus controls. Si milar results were obtained by ELISA testing supernatants from mitogen-stim ulated, unfractionated peripheral blood mononuclear cell (PBMC) cultures. I nterferon-alpha treatment was associated with a reduction in the mitogen-in duced Th1 cytokine response in those patients who cleared their plasma HCV- RNA. Analysis of cytokine expression by CD4 + T cells after HCV core antige n stimulation in a subgroup of 13 chronic hepatitis C patients demonstrated no cytokine response in 74% of these patients and an IFN-gamma -restricted response in 26%. Finally, no Th2 shift was found in lipopolysaccharide-sti mulated monocytes. These data indicate that a Th1 to Th2 shift does not occ ur in chronic hepatitis C.