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Infect Immun. 1972 September; 6(3): 344-347
Copyright © 1972 American Society for Microbiology. All Rights Reserved.

Interferon Production Linked to Toxicity of Polyriboinosinic Acid-Polyribocytidylic Acid

Erik de Clercq1, William E. Stewart II and Pierre de Somer

a Rega Institute for Medical Research, University of Leuven, 3000 Leuven, Belgium

ABSTRACT

Different procedures have been used in attempts to increase the production of interferon by polyriboinosinic acid-polyribocytidylic acid (poly [rI]·poly [rC]) in mice: simultaneous injection of lead acetate, cycloheximide, or actinomycin D and prior injection of Freund's adjuvant, chlorite-oxidized oxyamylose (COAM), endotoxin, or Brucella abortus. In the experimental conditions tested, lead acetate, cycloheximide, Freund's adjuvant, and COAM brought about a parallel increase in interferon production and toxicity (lethality) of poly (rI)·poly (rC); actinomycin D, endotoxin, and B. abortus increased the lethality of poly (rI)·poly (rC) without a concomitant raise of its interferon-inducing capacity. Our results indicate that no significant increase in interferon production (or antiviral activity, as far as the antiviral activity is accounted for by interferon production) without an accompanying increase in toxicity can be achieved with poly (rI)·poly (rC) and that it might be impossible to increase its therapeutic ratio (ratio of maximum tolerated dose to minimum effective dose).

FOOTNOTES

1 "Aangesteld Navorser" of the Belgian National Fonds voor Wetenschappelijk Onderzoek.

Infect Immun. 1972 September; 6(3): 344-347
Copyright © 1972 American Society for Microbiology. All Rights Reserved.





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