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

The effects of amantadine (1-5 mu M) and interferon alpha (IFN alpha)-2a al one (1000 IU/ml) and combined, have been studied in cultured peripheral blo od mononuclear cells (PBMC) from 15 chronic hepatitis C patients and ten he althy donors. Amantadine itself did not affect cell viability and had minor effects on the response to mitogens by PBMC. Four patients (27%), but no d onors, had hepatitis C virus (HCV) core and NS3-specific proliferative resp onses. Amantadine suppressed these responses in all cases and its antiproli ferative effect was greater than that of IFN alpha (Mann-Whitney's U-test: P < 0.05 in both cases). All PBMC cultures from patients, but none from don ors, were HCV RNA positive. Amantadine alone or combined with IFN alpha dos e-dependently reduced HCV RNA content in individual PBMC (Wilcoxon's signed rank test: 1 mu M, P < 0.05; 2 mu M, P < 0.02; and 5 mu M, P = 0.16) with respect to untreated cultures. In addition, 7, 13 and 20% of PBMC cultures became HCV RNA negative with 2 mu M amantadine alone, IFN alpha alone and t heir combination, respectively. Finally, in contrast to IFN alpha, amantadi ne did not modify expression of 2',5'-oligoadenylate synthetase activity or the spontaneous or mitogen-stimulated IFN gamma and interleukin 10 product ion. In conclusion, these effects in PBMC from HCV patients suggest that th e amantadine/IFN alpha combination might be considered a therapeutic option for treating chronic hepatitis C patients. (C) 1999 Elsevier Science B.V. All rights reserved.