Mechanism of Interferon Induction by Endotoxin

Abstract

When 1-kg rabbits received iv 500 µg of Boivin Escherichia coli endotoxin and were sacrificed 15 min later, production of interferon, as monitored by incubation of tissue slices in vitro, occurred primarily in the spleen, lung, liver, and thymus. When the temperature of incubation was 23 C, more interferon was produced than at 37 C. If the animals received 1 mg of actinomycin/kg 1 hr before administration of endotoxin, interferon production was accentuated in the spleen and lung. However, if the dose was increased to 5 mg/kg, no detectable interferon was produced. Production of interferon in slices was reversibly inhibited by cycloheximide or puromycin and was marginally accentuated after removal of these substances. These findings suggest that induction of interferon production by endotoxin, like induction by polyriboinosinic:polyribocytidylic acid (poly I:C) or virus, requires synthesis of messenger RNA and protein. Accentuated production by a marginal dose of actinomycin is explained by inhibited synthesis of messenger RNA for a control protein that inhibits interferon synthesis, as has been postulated for induction of interferon by poly I:C and by viruses.