Superinduction of Interferon with Metabolic Inhibitors: Possible Mechanisms and Practical Applications

Ten years have passed since cycloheximide was first shown to enhance endotoxininduced production of interferon in mice, in the first demonstration of what was later called the superinduction of interferon. Various inhibitors of protein and RNA synthesis, as well as combinations of these inhibitors,...

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Bibliographic Details
Published in:The Journal of infectious diseases 1976-06, Vol.133 (Supplement-2), p.A22-A29
Main Authors: Vilček, J., Havell, E. A., Kohase, M.
Format: Article
Language:English
Subjects:
Actinomycin
Animals
Antimetabolites - pharmacology
Cells, Cultured
Cultured cells
Cycloheximide - pharmacology
Dactinomycin - pharmacology
Diploidy
DNA - biosynthesis
Enzyme Induction - drug effects
Fibroblasts
Fibroblasts - drug effects
Humans
In Vitro Techniques
Interferon Inducers
Interferon: Properties and Production
Interferons
Interferons - biosynthesis
Interferons - blood
Interferons - radiation effects
Kidney cells
Leukocytes
Leukocytes - drug effects
Messenger RNA
Mice
Models, Biological
Protein synthesis
Rabbits
Ultraviolet Rays
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Summary:Ten years have passed since cycloheximide was first shown to enhance endotoxininduced production of interferon in mice, in the first demonstration of what was later called the superinduction of interferon. Various inhibitors of protein and RNA synthesis, as well as combinations of these inhibitors, have been shown to act as superinducing agents of interferon production stimulated by polyriboinosinicpolyribocytidylic 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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/133.Supplement_2.A22