MxA gene expression in peripheral blood mononuclear cells from patients infected chronically with hepatitis C virus treated with interferon-alpha.
Hepatitis C virus (HCV) infection causes acute and often chronic liver disease. The treatment of choice is interferon-alpha (IFN-alpha). The proportion of patients responding to therapy in terms of a sustained virological response, however, is relatively low. One possible reason for the lack of effectiveness might be neutralization of the drug by host's inhibitory factors. Recent kinetic studies suggested that high doses of IFN-alpha-, especially during the initial phase of therapy, might improve the virological response rates. Eighteen patients infected chronically with HCV were treated with IFN-alpha either at a standard dose (3 x 10(6) to 6 x 10(6) IU IFN-alpha three times weekly) for 6 to 12 months or with an intensified therapy (6 x 10(6) IU IFN-alpha daily) for at least one month. As surrogate parameter for the intracellular effect of the drug, MxA gene expression was quantified in RNA preparations from peripheral blood mononuclear cells. Beta-2-microglobulin (beta2M) concentrations were measured in serum. Serum HCV RNA titers were monitored in parallel. When compared to healthy individuals, untreated patients infected chronically with HCV were found to express 2.8-fold higher amounts of MxA specific transcripts. MxA gene expression and serum beta2M concentrations were found to be induced after administration of IFN-alpha, independent of the virological response not only during the initial phase of the intensified therapy but also over several months during standard therapy. It is concluded from these results that both early non-effectiveness of high dose IFN-alpha therapy as well as long-term non-effectiveness of standard therapy are not due to IFN-alpha inhibitory or neutralizing elements in serum.
Meier
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V
Georg-August-Universität Göttingen, Zentrum Innere Medizin, Abteilung für Gastroenterologie und Endokrinologie, Germany.
Mihm
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S
Ramadori
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G
D000328:Adult; D005260:Female; D019204:GTP-Binding Proteins; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001613:beta 2-Microglobulin / Q000097:blood
D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D001613:beta 2-Microglobulin; D019204:GTP-Binding Proteins