The target cells of injected type I interferons in mouse liver

Type I interferons (IFNs) have been used for the treatment of viral hepatitis, but it is unclear which cells in the liver are affected by injected IFN. The effects of IFN have been studied by the production of 2',5'-oligoadenylate synthetase (2'5'OAS), an IFN-inducible enzyme. Here, we studied the distribution of 2'5'OAS in mouse liver after injection of natural mouse IFN-alpha/beta by Western blotting and immunohistochemistry using a monoclonal antibody specific to mouse 42-kDa 2'5'OAS. Injection of IFN-alpha/beta increased the levels of liver 2'5'OAS and enhanced the intensities of immunohistochemical staining for this enzyme in both hepatocytes and Kupffer cells. In IFN-untreated normal mice, hepatocytes were lightly stained, but some of the Kupffer cells showed rather strong staining. The 2'5'OAS-positive Kupffer cells comprised approximately 60% of those in normal liver, whereas this increased to approximately 90% following IFN-alpha/beta injection. Thus, hepatocytes and Kupffer cells were the targets of injected IFN.