Superinduction of interferon with metabolic inhibitors: possible mechanisms and practical applications

Abstract

Ten years have passed since cycloheximide was first shown to enhance endotoxin-induced production of interferon in mice, in the first demonstration of what was later called the superinduction of interferon. Various inhibitors of protein and RNA symthesis, as well as combinations of these inhibitors, have been shown to act as superinducing agents of interferon production stimulated by polyriboinosinic-polyribocytidylic acid. The evidence that superinduction is due to the suppression of a mechanism of post-transcriptional regulation of interferon synthesis is rather convincing. The notion (first proposed about six years ago) that this modification is caused by a protein "repressor" remains the most plausible, albeit still unproved, hypothesis. The availability of systems that translate with fidelity interferon messenger RNA isolated from induced cells should prove most useful in the elucidation of post-transcriptional control mechanisms of interferon synthesis and of interferon superinduction. Meanwhile, superinduction has become a useful tool for the production of large quantities of interferon. In particular, this technique has been successfully applied to the production of interferon from human diploid fibroblasts. The clinical potential of this material remains to be critically examined.