Inhibition of RNA Synthesis in Human Lymphoid Cells Induces Interferon Production

Abstract

Human lymphoid cell cultures produced an interferon-like activity in the absence of inducers. Using actinomycin D, cycloheximide, and other metabolic inhibitors, we have shown that the cellular requirement for de novo RNA synthesis is not a requisite for interferon induction. We show here that the production of an interferon-like protein may be triggered in cultured lymphoid cells by substances capable of suppressing DNA-dependent RNA synthesis. Our data suggest that a rapidly turning over regulatory mechanism controls the production of an interferon-like molecule in lymphoid cells. In fact, the induction by inhibitors of RNA synthesis and the requirement for protein synthesis for production, but not for induction, suggests a preformed messenger RNA for an interferon-like molecule whose translation is normally prevented by a rapidly turning over mechanism which requires ongoing RNA synthesis. Experiments with neutralizing antibody for interferon suggest a new antigenic type of immune interferon or a slightly different molecule with lowered affinity for antibody. The very existence, however, of such a rapidly activated regulation of interferon production infers an important role in lymphocyte response and immune regulation.