The Effect of Actinomycin D on the Lethality of Poly I:C

Poly I:C, a synthetic double-stranded RNA composed of polyinosinic and polycytidylic acids, has become the subject of intense investigation because of its capacity to induce interferon formation and exert antineoplastic activity in experimental animals (1–4). It is currently being evaluated for possible antitumor activity in humans (4). A number of recent reports have shown that poly I:C simulates bacterial endotoxin in many of its activities (2–5), and shares several of the toxic properties of endotoxin (2, 6–9). For example, in addition to their capacity to stimulate interferon production (2), both poly I:C and endotoxin are pyrogenic (6) and embryotoxic (7), and provoke the Shwartzman phenomenon (8). It has been suggested that an inherent relationship exists between interferon induction and toxicity (2, 9). A further similarity in the action of poly I:C and endotoxin is the observation that several agents, such as bacillus Calmette-Guérin (BCG) vaccine, lead acetate, and zymosan, which augment the lethality of endotoxin, exert a similar effect on poly I:C (2).