Interferon-stimulated gene expression and hepatitis C viral dynamics during different interferon regimens.
OBJECTIVE
To address the molecular mechanism for enhanced antiviral efficacy associated with a frequent dosing of interferon (IFN)-beta.


METHODS
Serum hepatitis C viral (HCV) dynamics, double-stranded RNA-activated protein kinase (PKR) mRNA and MxA mRNA levels in peripheral blood mononuclear cells (PBMC) were analyzed serially in 140 patients who were randomly assigned to a twice daily (3 MU bid) or once daily (6 MU qd) administration group.


RESULTS
In twice daily group, the rate of HCV decline during the second phase was 2-fold greater than in the once daily group (P=0.04). Peak PKR and MxA gene expression levels in the first phase (observed 4 h after a single administration) were 2-fold higher in the once daily group. However, the expression in the second phase was maintained at a significantly higher level in the twice daily group. Initial and peak expression levels were related to initial viral load. Basal expressions in PBMC were significantly correlated with those in the liver tissue (PKR, r=0.81; MxA, r=0.75, respectively, P<0.0001).


CONCLUSIONS
Our data suggest that elimination of HCV-infected cells is enhanced by twice daily dosing of IFN-beta, and that this enhanced effect is associated with a higher intracellular expression of PKR and MxA during the second phase.
Asahina
Yasuhiro
Y
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan.
Izumi
Namiki
N
Uchihara
Masakatsu
M
Noguchi
Osamu
O
Nishimura
Yuki
Y
Inoue
Kazunari
K
Ueda
Ken
K
Tsuchiya
Kaoru
K
Hamano
Kosei
K
Itakura
Jun
J
Miyake
Shozo
S
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage*; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000097:blood; D019562:Viral Load; D019892:eIF-2 Kinase / Q000235:genetics
D000998:Antiviral Agents; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta; D019892:eIF-2 Kinase; D019204:GTP-Binding Proteins