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Human interferon production: superinduction by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole

P B Sehgal, I Tamm, J Vilcek

    Science (New York, N.Y.)
    |October 17, 1975
    PubMed

    Insights

    Polyinosinic.polycytidylic acid (poly(I.C)) boosts interferon production in human fibroblasts. The drug DRB significantly enhances this effect by inhibiting RNA synthesis, leading to prolonged interferon release.

    Area of Science:

    • Virology
    • Molecular Biology
    • Immunology

    Background:

    • Interferon production is crucial for antiviral defense.
    • Polyinosinic.polycytidylic acid (poly(I.C)) is a known inducer of interferon.
    • Understanding factors that enhance interferon production is key to developing antiviral therapies.

    Purpose of the Study:

    • To investigate the effect of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) on poly(I.C)-induced interferon production.
    • To explore the mechanism by which DRB enhances interferon synthesis.
    • To assess the duration and reversibility of DRB's superinducing effect.

    Main Methods:

    • Human diploid fibroblasts (FS-4) were treated with poly(I.C) and varying concentrations of DRB.
    • Interferon production was measured over a 24-hour period.
    • RNA synthesis inhibition by DRB was assessed.
    • The effect of DRB removal on interferon production was studied.

    Main Results:

    • DRB enhanced poly(I.C)-induced interferon production by up to 128-fold.
    • A strong correlation was observed between DRB's inhibition of RNA synthesis and its superinducing effect.
    • Interferon production continued for up to 4 days in the presence of DRB.
    • Removal of DRB promptly halted interferon production.

    Conclusions:

    • DRB acts as a potent superinducer of interferon production in human fibroblasts.
    • The mechanism of DRB's action involves the inhibition of nuclear heterogeneous RNA synthesis.
    • DRB treatment allows for sustained interferon production, with potential for controlled release upon drug withdrawal.

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