Relationship between 24-hour rhythm in antiviral effect of interferon-β and interferon-α/β receptor expression in mice

The influence of interferon-β (IFN-β) dosing time on antiviral activity was investigated in ICR male mice under light-dark cycle conditions (lights on at 07:00, off at 19:00) with food and water available ad libitum. There was a significant dosing time-dependent change in 2′,5′-oligoadenylate synthetase (2′,5′-OAS) activities, as an index of antiviral activity, in liver at 12 h after IFN-β (15 MIU/kg, i.v.) injection. IFN-β-induced 2′,5′-OAS activity was more potent after the drug injection during the late dark phase. The higher antiviral effect of IFN-β was observed when the interferon-α/β receptor (IFNAR) expression in the liver increased, and the lower effect was observed when its expression decreased. IFN-β-induced fever was more serious after IFN-β injection from the late dark phase to the early light phase. A significant dosing time-dependent change was demonstrated for plasma IFN-β concentrations, which showed a higher level during the light phase and a lower level during the dark phase. The dosing time-dependent change of plasma IFN-β concentrations was not associated with that of the antiviral effect or fever induced by IFN-β. These results suggest that selecting the most suitable dosing time of IFN-β, associated with the 24-h rhythm of IFNAR expression in the liver, may be important to increase effectively the antiviral activity of the drug in experimental and clinical situations.