Cells expressing a2-interferon were identified by indirect immunofluorescence using both a polyclonal and a monoclonal anti-a-interferon antibody reagent. In hepatitis B or delta virus infection, focal clusters of ainterferon-positive infiltrating mononuclear cells and (to a lesser extent) fibroblasts were regularly seen in liver sections from patients who had chronic active hepatitis and cirrhosis and evidence of virus replication, but in a minority of patients with chronic persistent hepatitis B and not in nonvirally infected livers. This report provides evidence for local a-interferon production near the site of virus replication in hepatitis B infection, identifies mononuclear cells and fibroblasts (but not hepatocytes) as the main cell types producing interferon in this infection and suggests that locally produced a-interferon may be a natural regulator of virus replication in HBsAg-positive chronic active hepatitis. Furthermore, serological characterization of the interferon species produced locally may predict which particular interferon species could be of the greatest therapeutic benefit in specific disease states or individual patients.
Considerable experimental evidence supports the view that interferon (IFN), produced naturally during virus infection, can limit the spread of virus and assist recovery [summarized in (111. In studying specific examples, it is clear that local tissue levels of IFN may vary widely in parallel with levels of virus replication and need not be reflected in serum IFN levels (2). In addition, although many different cell types are capable of producing IFN after in vitro stimulation (3-5), little is known about the cell types expressing IFN in natural disease states.
In at least one published report, serum IFN levels were found to be raised in patients with acute uncomplicated hepatitis A, B or non-A, non-B virus infection (6). In the same study, serum IFN levels were not found to be raised in patients with fulminant hepatitis, and the ability of peripheral mononuclear cells to produce IFN in vitro after stimulation in these subjects was markedly de-