Stimulation of antiviral activities of interferon by a liver extract preparation

The liver extract preparation Adelavin9 (referred to as EXT-FAD hereinafter) is a combination product that consists of hog liver extract and flavin-adenine dinucleotide (FAD). EXT-FAD has been reported to improve the histology of chronic liver injury and is widely used in Japan. Interferon (IFN) has been used to treat viral hepatitis. In this study, the action of EXT-FAD on the antiviral activity of IFN was examined using experimental models of viral infection in vitro and in vivo. EXT-FAD significantly enhanced the 2',5'-oligoadenylate synthetase (2-5AS) activity in human peripheral blood mononuclear cells (PBMC) treated with human IFN-alpha-2a. EXT-FAD is likely to affect the late phase of IFN action to produce the antiviral activity. Combination of IFN-alpha-2a with EXT-FAD produced a synergistic inhibitory effect against herpes simplex virus type-1 (HSV-1) in vitro. The effect of EXT-FAD in combination with IFN-alpha-2a against influenza virus type A (Fluv A) was also examined and a similar effect to that found in the anti-HSV-1 assay was observed. In addition, administration of EXT-FAD to mice infected with HSV-1 significantly prolonged the mean survival periods. The intracellular redox state plays a role in inhibiting virus replication. EXT-FAD was found to increase the intracellular glutathione (GSH) level. EXT-FAD also enhanced the nitric oxide synthase (NOS) activity, which plays a role in antiviral effects. This result indicate that the effect of EXT-FAD on the antiviral activity of IFN is partially related to increased intracellular GSH levels and NOS activation.