Do the interferons act singly or in combination?

Our views of interferon production and action have evolved from the simple to the complex. We review evidence that interferon-gamma (IFN-gamma) may induce a portion of its antiviral activity through the induction of another interferon. This is shown by demonstrating IFN-alpha in the supernatant fluids of IFN-gamma-treated mouse cells and showing that, under certain conditions, the antiviral activity of IFN-gamma in mouse and human cells can be reduced by antibody to IFN-alpha or IFN-beta, respectively. Induction of mouse spleen, bone marrow, and peritoneal exudate cells also results in their production of IFNs-alpha and/or -beta. In addition, new preliminary data indirectly suggests the presence of IFN-gamma in poly(IC):poly(LC)-treated mouse cells. In both of these systems, the maximal antiviral activity appears to develop as a consequence of the induction of a second interferon.