Induction of Interferon by Endotoxin

  • Monto Ho


The ability of bacterial endotoxin to modify virus infections was well documented before it was found it could induce interferon. Endotoxin decreased both the toxicity and the replication of some viruses. Hook and Wagner (1959) found that as little as 0.008 μg of purified E. coli lipopolysaccharide (LPS) inoculated intracerebrally in mice 75 min to 31/2 hr before an intracerebral challenge of 3–8 LD50 of WS influenza virus decreased the direct neurotoxic effects of this virus. Typhoid vaccine was similarly effective. This protective effect lasted for about 7 days. No effect on viral multiplication in the brain was found.


Newcastle Disease Virus Bacterial Endotoxin Interferon Production Brucella Abortus Interferon Induction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Atkins, E., 1960, Pathogenesis of fever, Physiol. Rev. 40:580.PubMedGoogle Scholar
  2. Atkins, E., and Francis, L., 1978, Pathogenesis of fever in delayed hypersensitivity: Factors influencing release of pyrogen-inducing lymphokines, Infect. Immun. 21:806.PubMedGoogle Scholar
  3. Atkins, E., Bodel, P., and Francis, L., 1967, Release of an endogenous pyrogen in vitro from rabbit mononuclear cells, J.Exp. Med. 126:357.PubMedCrossRefGoogle Scholar
  4. Beeson, P. B., 1948, Temperature-elevating effect of a substance obtained from polymorphonuclear leucocytes, J.Clin. Invest. 27:524.PubMedGoogle Scholar
  5. Bennett, I. L., 1964, Approaches to the mechanism of endotoxin action, in: Bacterial Endotoxins (M. Landy and W. Braun, eds.), pp. xiii-xiv, Rutgers University Press, New Brunswick, N.J.Google Scholar
  6. Bernheim, H. A., Block, L. H., and Atkins, E., 1979, Fever: Pathogenesis, physiology and purpose, Ann. Intern. Med. 91:261.PubMedGoogle Scholar
  7. Billiau, A., 1969, Systemic induction of interferon, Thesis for degree of geaggregeerde bij bet Hoger Onderwijs, University of Leuven, Belgium.Google Scholar
  8. Bodel, P. T., and Atkins, E., 1966, Human leucocyte pyrogen producing fever in rabbits, Proc. Soc. Exp. Biol. Med. 121:943.PubMedGoogle Scholar
  9. Borecky, L., 1968, Interferon induction by non-viral agents, in: Medical and Applied Virology (M. Sanders and E. H. Lennette, eds.), p. 181, Green, Missouri.Google Scholar
  10. Cantell, K., and Paucker, K., 1963, Quantitative studies on viral interference in suspended L-cells. IV. Production and assay of interferon, Virology 21:11.PubMedCrossRefGoogle Scholar
  11. Dinarello, C. A., Renfer, L., and Wolff, S. M., 1977, The production of antibody against human leucocytic pyrogen, J. Clin. Invest. 60:456.CrossRefGoogle Scholar
  12. Feingold, D. S., Keleti, G., and Youngner, J. S., 1976, Antiviral activity of Brucella abortus preparations: Separation of active components, Infect. Immun. 13:763.PubMedGoogle Scholar
  13. Field, A. K., Tytell, A. A., Lampson, G. P., and Hilleman, M. R., 1968, Inducers of interferon and host resistance. V. In vitro studies, Proc. Natl. Acad. Sci. USA 61:340.PubMedCrossRefGoogle Scholar
  14. Finkelstein, M. S., Bausek, G. H., and Merigan, T. C., 1968, Interferon inducers in vitro: Difference in sensitivity to inhibitors of RNA and protein synthesis, Science 161:465.PubMedCrossRefGoogle Scholar
  15. Gledhill, A. W., 1959a, The effect of bacterial endotoxin on resistance of mice to ectro-melia, Br. J. Exp. Pathol. 40:195.PubMedGoogle Scholar
  16. Gledhill, A. W., 1959b, Sparing effect of serum of mice treated with endotoxin upon certain murine virus diseases, Nature (London) 183:185.CrossRefGoogle Scholar
  17. Gledhill, A. W., 1959c, The interference of mouse hepatitis virus with ectromelia in mice and a possible explanation of its mechanism, Br. J. Exp. Pathol. 40:291.PubMedGoogle Scholar
  18. Gledhill, A. W., 1964, Influence of endotoxin upon the pathogenesis of viral infections, in: Bacterial Endotoxins (M. Landy and W. Braun, eds.), p. 410, Rutgers University Press, New Brunswick, N.J.Google Scholar
  19. Hahn, H. H., Char, D. C., Posteli, W. B., and Wood, W. B., Jr., 1967, Studies on the pathogenesis of fever. XV. The production of endogenous pyrogen by peritoneal macrophages, J.Exp. Med. 126:385.PubMedCrossRefGoogle Scholar
  20. Hallum, J. V., Youngner, J. S., and Stinebring, W. R., 1965, Interferon activity associated with high molecular weight proteins in the circulation of mice injected with endotoxin or bacteria, Virology 27:429.PubMedCrossRefGoogle Scholar
  21. Ho, M., 1964a, Identification and induction of interferon, Bacteriol. Rev. 28:367.PubMedGoogle Scholar
  22. Ho, M., 1964b, Interferon-like viral inhibitor in rabbits after intravenous administration of endotoxin, Science 146:1472.PubMedCrossRefGoogle Scholar
  23. Ho, M., 1981, Induction of the interferon protein in the animal: General considerations, in: The Interferon System: A Review to 1982 (S. Baron, F. Dianzani, and J. Stanton, eds.), Texas Reports on Biology and Medicine, in press.Google Scholar
  24. Ho, M., and Armstrong, J. A., 1975, Interferon, Annu. Rev. Microbiol. 29:131.PubMedCrossRefGoogle Scholar
  25. Ho, M., and Kass, E. H., 1958, Protective effect of components of normal blood against the lethal action of endotoxin, J. Clin. Med. 51:297.Google Scholar
  26. Ho, M., and Ke, Y. H., 1970, The mechanisms of stimulation of interferon production by a complexed polyribonucleotide, Virology 40:683.CrossRefGoogle Scholar
  27. Ho, M., and Kono, Y., 1965a, Effect of antinomycin D on virus and endotoxin-induced interferon-like inhibitors in rabbits, Proc. Natl. Acad. Sci. USA 53:220.PubMedCrossRefGoogle Scholar
  28. Ho, M., and Kono, Y., 1965b, Tolerance to the induction of interferons by endotoxin and virus, J. Clin. Invest. 44:1059.Google Scholar
  29. Ho, M., and Postic, B., 1967, Prospects for applying interferon to man, PAHO/WHO Scientific Publication 147, pp. 632–649, Washington, D.C.Google Scholar
  30. Ho, M., Kono, Y., and Breinig, M. K., 1965, Tolerance to the induction of interferon by endotoxin and virus: Role of a humoral factor, Proc. Soc. Exp. Biol. Med. 119:1227.PubMedGoogle Scholar
  31. Ho, M., Breinig, M. K., Postic, B., and Armstrong, J. A., 1970, Effect of preinjections on the stimulation of interferon by a complexed polynucleotide, endotoxin and virus, Ann. N.Y. Acad. Sci. 173:680.CrossRefGoogle Scholar
  32. Ho, M., Ke, Y. H., and Armstrong, J. A., 1973, Mechanism of interferon induction by endotoxin, J.Infect. Dis. 128(Suppl.):220.PubMedCrossRefGoogle Scholar
  33. Hook, E. W., and Wagner, R. R., 1959, The resistance-promoting activity of endotoxins and other microbial products. II. Protection against the neurotoxic action of influenza virus, J.Immunol. 83:310.PubMedGoogle Scholar
  34. Ito, Y., Nagata, I., and Kunii, A., 1973, Mechanism of endotoxin-type interferon production in mice, Virology 52:439.PubMedCrossRefGoogle Scholar
  35. Jullien, P., and DeMaeyer, E., 1966, Interferon synthesis in X-irradiated animals. I. Depression of circulating interferon in C3H mice after whole body irradiation, Int. J. Radiat. Biol. 11:567.CrossRefGoogle Scholar
  36. Kadish, A. S., Tansey, F. A., Yu, G. S. M., Doyle, A. T., and Bloom, B. R., 1980, Interferon as a mediator of human lymphocyte suppression, J.Exp. Med. 151:637.PubMedCrossRefGoogle Scholar
  37. Kawada, Y., Yamamoto, Y., Fujisawa, J., and Watanabe, Y., 1980, Antigenic relationships among various interferon species, Ann. N.Y. Acad. Sci. 350:422.CrossRefGoogle Scholar
  38. Ke, Y. H., Ho, M., and Merigan, T. C., 1966a, Heterogeneity of rabbit serum interferons, Nature (London) 211:541.CrossRefGoogle Scholar
  39. Ke, Y. H., Singer, S. H., Postic, B., and Ho, M., 1966b, Effect of puromycin on virus and endotoxin-induced interferonlike inhibitors in rabbits, Proc. Soc. Exp. Biol. Med. 121: 181.PubMedGoogle Scholar
  40. Kelcti, G., Feingold, D. S., and Youngner, J. S., 1974, Interferon induction in mice by lipopolysaccharide from Brucella abortus, Infec. Immun. 10:282.Google Scholar
  41. Kobayashi, S., Yasui, O., and Masuzumi, M., 1969, Studies on early-appearing interferon in vitro. I. Production of endotoxin-induced interferon by mouse spleen cells cultured in vitro, Proc. Soc. Exp. Biol. Med. 131:487.Google Scholar
  42. Laskovic, V., Borecky, L., Sike, D., Master, L., and Bauer, S., 1967, The temperature requirement for interferon production in cells stimulated by Newcastle disease virus or microbial agents in vitro, Acta Virol. (Engl. Ed.) 11:500.Google Scholar
  43. Likar, M., Bartley, E. O., and Wilson, D. C., 1959, Observations on the interaction of poliovirus and host cells in vitro. III. The effect of some bacterial metabolites and endotoxins, Br. J. Exp. Pathol. 40:391.PubMedGoogle Scholar
  44. Maehara, N., and Ho, M., 1977, Cellular origin of interferon induced by bacterial lipopolysaccharide, Infect. Immun. 15:78.PubMedGoogle Scholar
  45. Maehara, N., Ho, M., and Armstrong, J. A., 1977, Differences in mouse interferons according to cell source and mode of induction, Infect. Immun. 17:572.PubMedGoogle Scholar
  46. Michaels, R. H., Weinberger, M. M., and Ho, M., 1965, Circulating interferon-like viral inhibitor in patients with meningitis due to Haemophilus influenzae, N. Engl. J. Med. 272:1148.CrossRefGoogle Scholar
  47. Mickenberg, I. D., Root, R. K., and Wolff, S. M., 1972, Bactericidal and metabolic properties of human eosinophils, Blood 39:67.PubMedGoogle Scholar
  48. Postic, B., DeAngelis, C., Breinig, M. K., and Ho, M., 1966, Effect of temperature on the induction of interferons by endotoxin and virus, J.Bacteriol. 91:1277.PubMedGoogle Scholar
  49. Postic, B., DeAngelis, C., Breinig, M. K., and Ho, M., 1967, Effects of Cortisol and adrenalectomy on induction of interferon by endotoxin, Proc. Soc. Exp. Biol. Med. 125:89.PubMedGoogle Scholar
  50. Sauter, C., and Wolfensberger, C., 1980, Interferon in human serum after injection of endotoxin, Lancet 2:852.PubMedCrossRefGoogle Scholar
  51. Scott, G. M., Secher, D. S., Flowers, D., Bate, J., Cantell, K., and Tyrrell, D. A. J., 1981, Toxicity of interferon, Br. Med. J. 282:1345.CrossRefGoogle Scholar
  52. Skarnes, R. C., Rosen, F. S., Shear, M. J., and Landy, M., 1958, Inactivation of endotoxin by a humoral component. II. Interaction of endotoxin with serum and plasma. J. Exp. Med. 108:685.PubMedCrossRefGoogle Scholar
  53. Smith, T. J., and Wagner, R. R., 1967, Rabbit macrophage interferon. I. Conditions for biosynthesis of virus-infected and uninfected cells, J.Exp. Med. 125:559.PubMedCrossRefGoogle Scholar
  54. Staub, H. M., 1965, Bacterial lipido-proteino-polysaccharide (“O” somatic antigens) extracted with trichloroacetic acid, in: Methods in Carbohydrate Chemistry (R. L. Whistler, J. N. BeMiller, and M. L. Wolfram, eds.), Vol. 5, pp. 92–93, Academic Press, New York.Google Scholar
  55. Stewart, W. E., II, 1979, The Interferon System, Springer-Verlag, Berlin.Google Scholar
  56. Stinebring, W. R., and Youngner, J. S., 1964, Patterns of interferon appearance in mice injected with bacteria or bacterial endotoxin, Nature (London) 204:712.CrossRefGoogle Scholar
  57. Suter, E., and Kirsanow, E. M., 1961, Hyperreactivity to endotoxin in mice infected with mycobacteria — Induction and elicitation of the reactions, Immunology 4:354.PubMedGoogle Scholar
  58. Tan, Y. H., Armstrong, J. A., Ke, Y. H., and Ho, M., 1970, Regulation of cellular interferon production: Enhancement by antimetabolites, Proc. Natl. Acad. Sci. USA 67:464.PubMedCrossRefGoogle Scholar
  59. Trinchieri, G., and Santoli, D., 1978, Anti-viral activity induced by culturing lymphocytes with tumor derived or virus-transformed cells: Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis, J.Exp. Med. 147:1314.PubMedCrossRefGoogle Scholar
  60. Vilcek, J., 1970, Metabolic determinants of the induction of interferon by a synthetic double-stranded polynucleotide in rabbit kidney cells, Ann. N.Y. Acad. Sci. 173:390.CrossRefGoogle Scholar
  61. Wagner, R. R., 1955, Cytotoxic action of influenza virus: Failure to induce acquired resistance phenomenon in tissue culture, Proc. Soc. Exp. Biol. Med. 90:214.PubMedGoogle Scholar
  62. Wagner, R. R., Snyder, R. M., Hook, E. W., and Luttrell, C. N., 1959, Effect of bacterial endotoxin on resistance of mice to viral encephalitides, J. Immunol. 83:87.PubMedGoogle Scholar
  63. Westphal, O., and Jann, K., 1965, Bacterial lipopolysaccharides: Extraction with phenol-water and further application of the procedure, in: Methods in Carbohydrate Chemistry (R. L. Whistler, J. N. BeMiller, and M. L. Wolfram, eds.), Vol. 5, pp. 83–91, Academic Press, New York.Google Scholar
  64. Youngner, J. S., and Feingold, D. S., 1967, Interferon production in mice by cell wall mutants of Salmonella typhimunum, J. Virol. 1:1164.Google Scholar
  65. Youngner, J. S., and Hallum, J. V., 1968, Interferon production in mice by double-stranded synthetic polynucleotides: Induction or release?, Virology 35:177.PubMedCrossRefGoogle Scholar
  66. Youngner, J. S., and Salvin, S. B., 1973, Production and properties of migration inhibitory factor and interferon in the circulation of mice with delayed hypersensitivity, J. Immunol. 111:1914.PubMedGoogle Scholar
  67. Youngner, J. S., and Stinebring, W. R., 1964, Interferon production in chickens injected with Brucella abortus, Science 144:1022.Google Scholar
  68. Youngner, J. S., and Stinebring, W. R., 1965, Interferon appearance stimulated by endotoxin, bacteria, or viruses in mice pretreated with Escherichia coli endotoxin or infected with Mycobacterium tuberculosis, Nature (London) 208:456.CrossRefGoogle Scholar
  69. Youngner, J. S., Stinebring, W. R., and Taube, S. G., 1965, Influence of inhibitors of protein synthesis on interferon formation in mice, Virology 27:541.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Monto Ho
    • 1
    • 2
  1. 1.Department of MicrobiologyGraduate School of Public HealthPittsburghUSA
  2. 2.Department of Medicine, School of MedicineUniversity of PittsburghPittsburghUSA

Personalised recommendations