Regulation of interferon production. Superinduction by dihydrorifampicin in human and chick embryo fibroblasts and mouse L929 cells.

Dihydrorifampicin (DHR), a new reversible inhibitor of RNA polymerases I and II in eukaryotic cells, exhibited a very high enhancing effect on the production of interferon (IFN) in cultures of human and chick embryo fibroblasts and mouse L929 cells induced by poly(I). poly(C). The titres of interferon produced in human fibroblast cultures superinduced with poly(I). poly(C), cycloheximide and DHR were 128 times higher as compared with cultures treated with poly(I). poly(C) only. A similar superinduction of interferon by DHR was observed in mouse and chicken cell cultures, IFN titres in culture media were 40-60 times higher in comparison with cultures treated only with the inducer. In comparison with actinomycin D in the superinduction experiments, DHR was not toxic and allowed much higher yields of IFN. The use of DHR may be especially advantageous for the superinduction and production of human fibroblast IFN in cultures of human diploid fibroblasts.