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.
Martín
J
J
Department of Hepatology, Fundación Jiménez Díaz, Madrid, Spain.
Navas
S
S
Fernández
M
M
Rico
M
M
Pardo
M
M
Quiroga
J A
JA
Zahm
F
F
Carreño
V
V
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000547:Amantadine / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D014758:Viral Core Proteins / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D015088:2',5'-Oligoadenylate Synthetase; D000547:Amantadine; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007371:Interferon-gamma; D016753:Interleukin-10; D012367:RNA, Viral; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases