Interferon Production Linked to Toxicity of Polyriboinosinic Acid-polyribocytidylic Acid

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 1972 Sep 1

PMID 4564891

Citations 4

Authors

E De Clercq

W E Stewart 2nd

P DE SOMER

Affiliations

Soon will be listed here.

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).

Citing Articles

A microarray patch SARS-CoV-2 vaccine induces sustained antibody responses and polyfunctional cellular immunity.

Balmert S, Gholizadeh Ghozloujeh Z, Donahue Carey C, Williams L, Zhang J, Shahi P iScience. 2022; 25(10):105045.

PMID: 36062075 PMC: 9425707. DOI: 10.1016/j.isci.2022.105045.

Localized irradiation of tumors prior to synthetic dsRNA therapy enhanced the resultant anti-tumor activity.

Le U, Kaurin D, Sloat B, Yanasarn N, Cui Z Radiother Oncol. 2008; 90(2):273-9.

PMID: 19013656 PMC: 2741318. DOI: 10.1016/j.radonc.2008.10.016.

Suppression of extablished Friend virus leukemia by statolon: potentiation of statolon's leukemosuppressive activity by chlorite-oxidized oxyamylose.

Weislow O, Wheelock E Infect Immun. 1975; 11(1):129-36.

PMID: 1090523 PMC: 415035. DOI: 10.1128/iai.11.1.129-136.1975.

Antiviral and interferon-inducing activity of a new glutarimide antibiotic, 9-methylstreptimidone.

Saito N, Suzuki F, Sasaki K, Ishida N Antimicrob Agents Chemother. 1976; 10(1):14-9.

PMID: 984746 PMC: 429681. DOI: 10.1128/AAC.10.1.14.

References

Rice J, Turner W, Chirigos M, Rice N . Enhancement by poly-D-lysine of poly I: C-induced interferon production in mice. Appl Microbiol. 1970; 19(5):867-9. PMC: 376805. DOI: 10.1128/am.19.5.867-869.1970. View

Adamson R, Fabro S . Embryotoxic effect of poly I. poly C. Nature. 1969; 223(5207):718. DOI: 10.1038/223718a0. View

Zedeck M, Marquardt H, Sternberg S, Fleisher M, Hamilton L . Role of adrenal cortical function in toxicity of polyriboinosinic-polyribocytidylic acid and its component homopolymers. Proc Natl Acad Sci U S A. 1970; 67(1):180-4. PMC: 283185. DOI: 10.1073/pnas.67.1.180. View

Ostler H, Oh J, DAWSON C, Burt W . Toxicity of poly I: poly C for rabbit eyes. Nature. 1970; 228(5269):362-4. DOI: 10.1038/228362a0. View

De Clercq E, Nuwer M, Merigan T . Potentiating Effect of Freund's Adjuvant on Interferon Production by Endotoxin or Poly rI*Poly rC. Infect Immun. 1970; 2(1):69-76. PMC: 415966. DOI: 10.1128/iai.2.1.69-76.1970. View

De Clercq E, Nuwer M, Merigan T . The role of interferon in the protective effect of a synthetic double-stranded polyribonucleotide against intranasal vesicular stomatitis virus challenge in mice. J Clin Invest. 1970; 49(8):1565-77. PMC: 322636. DOI: 10.1172/JCI106374. View

Pieroni R, BUNDEALLY A, Levine L . The effect of actinomycin D on the lethality of poly I:C. J Immunol. 1971; 106(4):1128-9. View

Jullien P, De Maeyer-Guignard J . Toxic effect of polyriboinosinic-polyribocytidylic acid on mouse hemopoietic stem cells. Int J Cancer. 1971; 7(3):468-75. DOI: 10.1002/ijc.2910070312. View

LEONARD B, ECCLESTON E, Jones D . Toxicity of interferon inducers of the double stranded RNA type. Nature. 1969; 224(5223):1023-4. DOI: 10.1038/2241023a0. View

10.

Lindsay H, TROWN P, Brandt J, Forbes M . Pyrogenicity of poly I. poly C in rabbits. Nature. 1969; 223(5207):717-8. DOI: 10.1038/223717a0. View

11.

Chester T, De Clercq E, Nuwer M, Merigan T . In vivo release of previously cleared interferon by cycloheximide. Infect Immun. 1972; 5(3):383-8. PMC: 422379. DOI: 10.1128/iai.5.3.383-388.1972. View

12.

Steinberg A, Baron S, Talal N . The pathogenesis of autoimmunity in New Zealand mice, I. Induction of antinucleic acid antibodies by polyinosinic-polycytidylic acid. Proc Natl Acad Sci U S A. 1969; 63(4):1102-7. PMC: 223434. DOI: 10.1073/pnas.63.4.1102. View

13.

Bertok L . Effect of sulfhydryl compound on the lead acetate-induced endotoxin hypersensitivity of rats. J Bacteriol. 1968; 95(5):1974-5. PMC: 252239. DOI: 10.1128/jb.95.5.1974-1975.1968. View

14.

Vilcek J, Ng M . Post-transcriptional control of interferon synthesis. J Virol. 1971; 7(5):588-94. PMC: 356167. DOI: 10.1128/JVI.7.5.588-594.1971. View

15.

Young P, Taylor J, Yu M, Eyerman E . Morphological changes in chick cerebellum induced by poly I-poly C. Nature. 1970; 228(5277):1191-2. DOI: 10.1038/2281191a0. View

16.

Rice J, Turner W, Chirigos M, Spahn G . Dose responsiveness and variation among inbred strains of mice in production of interferon after treatment with poly (I)-poly (C) (poly-D-lysine) complexes. Appl Microbiol. 1971; 22(3):380-6. PMC: 376318. DOI: 10.1128/am.22.3.380-386.1971. View

17.

De Clercq E, Merigan T . Stimulation or inhibition of interferon production depending on time of cycloheximide administration. Virology. 1970; 42(3):799-802. DOI: 10.1016/0042-6822(70)90328-4. View

18.

Niblack J, McCreary M . Relationship of biological activities of poly I-poly C to homopolymer molecular weights. Nat New Biol. 1971; 233(36):52-3. DOI: 10.1038/newbio233052a0. View

19.

Absher M, Stinebring W . Toxic properties of a synthetic double-stranded RNA. Endotoxin-like properties of poly I. poly C, an interferon stimulator. Nature. 1969; 223(5207):715-7. DOI: 10.1038/223715a0. View

20.

Dianzani F, RITA G, Cantagalli P, Gagnoni S . Effect of DEAE-dextran on interferon production and protective effect in mice treated with the double-stranded polynucleotide complex polyinosinic-polycytidylic acid. J Immunol. 1969; 102(1):24-7. View