In vitro effect of amantadine and interferon alpha-2a on hepatitis C virus markers in cultured peripheral blood mononuclear cells from hepatitis C virus-infected patients.

The effects of amantadine (1-5 microM) and interferon alpha (IFNalpha)-2a alone (1000 IU/ml) and combined, have been studied in cultured peripheral blood mononuclear cells (PBMC) from 15 chronic hepatitis C patients and ten healthy donors. Amantadine itself did not affect cell viability and had minor effects on the response to mitogens by PBMC. Four patients (27%), but no donors, had hepatitis C virus (HCV) core and NS3-specific proliferative responses. Amantadine suppressed these responses in all cases and its antiproliferative effect was greater than that of IFNalpha (Mann-Whitney's U-test: P < 0.05 in both cases). All PBMC cultures from patients, but none from donors, were HCV RNA positive. Amantadine alone or combined with IFNalpha dose-dependently reduced HCV RNA content in individual PBMC (Wilcoxon's signed rank test: 1 microM, P < 0.05; 2 microM, P < 0.02; and 5 microM, P = 0.16) with respect to untreated cultures. In addition, 7, 13 and 20% of PBMC cultures became HCV RNA negative with 2 microM amantadine alone, IFNalpha alone and their combination, respectively. Finally, in contrast to IFNalpha, amantadine did not modify expression of 2',5'-oligoadenylate synthetase activity or the spontaneous or mitogen-stimulated IFNgamma and interleukin 10 production. In conclusion, these effects in PBMC from HCV patients suggest that the amantadine/IFNalpha combination might be considered a therapeutic option for treating chronic hepatitis C patients.