Abstract
Intraperitoneal injection of mice with mineral oil, incomplete (IFA) or complete Freund's adjuvant (CFA) increased the interferon response to endotoxin or (poly rI)•(poly rC) administered intravenously 2 days later. After endotoxin administration, circulating interferon titers were increased at several different times of sampling and with a variety of endotoxin dosages. When injection of endotoxin was delayed until 6 to 8 days after the administration of IFA or CFA, interferon production was markedly decreased. Mice treated with CFA and injected with endotoxin 2 days later became more resistant to intranasal vesicular stomatitis virus challenge than mice injected with endotoxin alone. Hyporeactivity to the interferon-inducing capacity of a second injection of endotoxin 2 days after the first injection could not be overcome by administering CFA simultaneously with the first dose. CFA treatment not only raised the serum interferon titers produced by endotoxin, but also increased the number of interferon-forming cells in the spleen after administration of endotoxin in vivo. In addition, CFA enhanced the intravascular clearance of (poly rI)•(poly rC). The possibility that Freund's adjuvant increased the interferon response to endotoxin and (poly rI)•(poly rC) by stimulating the uptake and processing of the interferon inducer by lymphoreticular cells is discussed.
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Selected References
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- Absher M., Stinebring W. R. Toxic properties of a synthetic double-stranded RNA. Endotoxin-like properties of poly I. poly C, an interferon stimulator. Nature. 1969 Aug 16;223(5207):715–717. doi: 10.1038/223715a0. [DOI] [PubMed] [Google Scholar]
- BIOZZI G., BENACERRAF B., GRUMBACH F., HALPERN B. N., LEVADITI J., RIST N. Etude de l'activité granulopexique du système réticulo-endothélial au cours de l'infection tuberculeuse expérimentale de la souris. Ann Inst Pasteur (Paris) 1954 Sep;87(3):291–300. [PubMed] [Google Scholar]
- Bausek G. H., Merigan T. C. Cell interaction with a synthetic polynucleotide and interferon production in vitro. Virology. 1969 Nov;39(3):491–498. doi: 10.1016/0042-6822(69)90097-x. [DOI] [PubMed] [Google Scholar]
- Berman L. D., Allison A. C., Pereira H. G. Effects of Freund's adjuvant on adenovirus oncogenesis and antibody production in hamsters. Int J Cancer. 1967 Sep 15;2(5):539–543. doi: 10.1002/ijc.2910020515. [DOI] [PubMed] [Google Scholar]
- CUTLER J. L. The enhancement of hemolysin production in the rat by Zymosan. J Immunol. 1960 Apr;84:416–419. [PubMed] [Google Scholar]
- DRESSER D. W. Effectiveness of lipid and lipidophilic substances as adjuvants. Nature. 1961 Sep 16;191:1169–1171. doi: 10.1038/1911169a0. [DOI] [PubMed] [Google Scholar]
- DRESSER D. W. Elimination of 131-I-labelled protein antigens from the circulation of the mouse. Immunology. 1960 Oct;3:289–295. [PMC free article] [PubMed] [Google Scholar]
- De Clercq E., Merigan T. C. An active interferon inducer obtained from Hemophilus influenzae type B. J Immunol. 1969 Nov;103(5):899–906. [PubMed] [Google Scholar]
- De Clercq E., Merigan T. C. Requirement of a stable secondary structure for the antiviral activity of polynucleotides. Nature. 1969 Jun 21;222(5199):1148–1152. doi: 10.1038/2221148a0. [DOI] [PubMed] [Google Scholar]
- De Somer P., Billiau A. Interferon production by the spleen of rats after intravenous injection of Sindbis virus or heat-killed Escherichia coli. Arch Gesamte Virusforsch. 1966;19(2):143–154. doi: 10.1007/BF01241494. [DOI] [PubMed] [Google Scholar]
- FREUND J. The effect of paraffin oil and mycobacteria on antibody formation and sensitization; a review. Am J Clin Pathol. 1951 Jul;21(7):645–656. doi: 10.1093/ajcp/21.7.645. [DOI] [PubMed] [Google Scholar]
- Finger H. Die Adjuvanswirkung von Mycobakterien. Klin Wochenschr. 1966 Oct 1;44(19):1105–1111. doi: 10.1007/BF01745533. [DOI] [PubMed] [Google Scholar]
- Fruitstone M. J., Michaels B. S., Rudloff D. A., Sigel M. M. Role of the spleen in interferon production in mice. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1008–1011. doi: 10.3181/00379727-122-31311. [DOI] [PubMed] [Google Scholar]
- Glasgow L. A. Leukocytes and interferon in the host response to viral infections. II. Enhanced interferon response of leukocytes from immune animals. J Bacteriol. 1966 Jun;91(6):2185–2191. doi: 10.1128/jb.91.6.2185-2191.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldner H., Girardi A. J., Hilleman M. R. Enhancement in hamsters of virus oncogenesis attending vaccination procedures. Virology. 1965 Oct;27(2):225–227. doi: 10.1016/0042-6822(65)90164-9. [DOI] [PubMed] [Google Scholar]
- Gorhe D. S. Inhibition of multiplication of foot and mouth disease virus in adult mice pretreated with Freund's complete adjuvant. Nature. 1967 Dec 23;216(5121):1242–1244. doi: 10.1038/2161242a0. [DOI] [PubMed] [Google Scholar]
- Green J. A., Cooperband S. R., Kibrick S. Immune specific induction of interferon production in cultures of human blood lymphocytes. Science. 1969 Jun 20;164(3886):1415–1417. doi: 10.1126/science.164.3886.1415. [DOI] [PubMed] [Google Scholar]
- Ho M., Kono Y., Breinig M. K. Tolerance to the induction of interferons by endotoxin and virus: role of a humoral factor. Proc Soc Exp Biol Med. 1965 Aug-Sep;119(4):1227–1232. doi: 10.3181/00379727-119-30421. [DOI] [PubMed] [Google Scholar]
- Johnson R. T., Mims C. A. Pathogenesis of viral infections of the nervous system. N Engl J Med. 1968 Jan 4;278(1):23–contd. doi: 10.1056/NEJM196801042780106. [DOI] [PubMed] [Google Scholar]
- MURAMATSU S. SHORTENING OF THE PERIOD OF PRIMARY IMMUNE RESPONSE BY THE PRIOR INJECTION OF FREUND'S ADJUVANT. Nature. 1964 Mar 14;201:1141–1142. doi: 10.1038/2011141a0. [DOI] [PubMed] [Google Scholar]
- Merigan T. C., Finkelstein M. S. Interferon-stimulating and in vivo antiviral effects of various synthetic anionic polymers. Virology. 1968 Jul;35(3):363–374. doi: 10.1016/0042-6822(68)90215-8. [DOI] [PubMed] [Google Scholar]
- Nicol T., Quantock D. C., Vernon-Roberts B. Stimulation of phagocytosis in relation to the mechanism of action of adjuvants. Nature. 1966 Mar 12;209(5028):1142–1143. doi: 10.1038/2091142b0. [DOI] [PubMed] [Google Scholar]
- Osborn J. E., Walker D. L. The role of individual spleen cells in the interferon response of the intact mouse. Proc Natl Acad Sci U S A. 1969 Apr;62(4):1038–1045. doi: 10.1073/pnas.62.4.1038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Postic B., DeAngelis C., Breinig M. K., Ho M. Effects of cortisol and adrenalectomy on induction of interferon by endotoxin. Proc Soc Exp Biol Med. 1967 May;125(1):89–92. doi: 10.3181/00379727-125-32021. [DOI] [PubMed] [Google Scholar]
- RIGGI S. J., DI LUZIO N. R. Identification of a reticuloendothelial stimulating agent in zymosan. Am J Physiol. 1961 Feb;200:297–300. doi: 10.1152/ajplegacy.1961.200.2.297. [DOI] [PubMed] [Google Scholar]
- Rodey G. E., Good R. A. Modification of the in vitro response to phytohemagglutinin of mouse spleen cells by amyloidogenic agents. Proc Soc Exp Biol Med. 1969 Jun;131(2):457–461. doi: 10.3181/00379727-131-33901. [DOI] [PubMed] [Google Scholar]
- SCHOENBERG M. D., GILMAN P. A., MUMAW V., MOORE R. D. Proliferation of the reticuloendothelial system and phagocytosis. Exp Mol Pathol. 1963 Apr;2:126–143. doi: 10.1016/0014-4800(63)90047-9. [DOI] [PubMed] [Google Scholar]
- SHEPEL M., KLUGERMAN M. R. EFFECT OF ADJUVANTS ON ANTIBODY RESPONSE OF RABBITS INOCULATED WITH VENEZUELAN EQUINE ENCEPHALOMYELITIS VIRUS. J Bacteriol. 1963 May;85:1150–1155. doi: 10.1128/jb.85.5.1150-1155.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siegel B. V., Morton J. I. Influence of immunologic hyperstimulation on murine viral leukemogenesis. Blood. 1967 Apr;29(4 Suppl):585–593. [PubMed] [Google Scholar]
- Subrahmanyan T. P., Mims C. A. Fate of intravenously administered interferon and the distribution of interferon during virus infections in mice. Br J Exp Pathol. 1966 Apr;47(2):168–176. [PMC free article] [PubMed] [Google Scholar]
- Van Rossum W., De Somer P. Some aspects of the interferon production in vivo. Life Sci. 1966 Jan;5(2):105–113. doi: 10.1016/0024-3205(66)90121-4. [DOI] [PubMed] [Google Scholar]
- White R. G. Role of adjuvants in the production of delayed hypersensitivity. Br Med Bull. 1967 Jan;23(1):39–45. doi: 10.1093/oxfordjournals.bmb.a070514. [DOI] [PubMed] [Google Scholar]
- Youngner J. S., Feingold D. S. Interferon production in mice by cell wall mutants of Salmonella typhimurium. J Virol. 1967 Dec;1(6):1164–1167. doi: 10.1128/jvi.1.6.1164-1167.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Youngner J. S., Hallum J. V. Interferon production in mice by double-stranded synthetic polynucleotides: induction or release? Virology. 1968 May;35(1):177–179. doi: 10.1016/0042-6822(68)90320-6. [DOI] [PubMed] [Google Scholar]
- Youngner J. S. Influence of inhibitors of protein synthesis on interferon formation in mice. II. Comparison of effects of glutarimide antibiotics and tenuazonic acid. Virology. 1970 Feb;40(2):335–343. doi: 10.1016/0042-6822(70)90410-1. [DOI] [PubMed] [Google Scholar]
- Youngner J. S., Stinebring W. R. Comparison of interferon production in mice by bacterial endotoxin and statolon. Virology. 1966 Jun;29(2):310–316. doi: 10.1016/0042-6822(66)90038-9. [DOI] [PubMed] [Google Scholar]
- Youngner J. S., Stinebring W. R. Interferon appearance stimulated by endotoxin, bacteria, or viruses in mice pre-treated with Escherichia coli endotoxin or infected with Mycobacterium tuberculosis. Nature. 1965 Oct 30;208(5009):456–458. doi: 10.1038/208456a0. [DOI] [PubMed] [Google Scholar]
- Youngner J. S., Stinebring W. R., Taube S. E. Influence of inhibitors of protein synthesis on interferon formation in mice. Virology. 1965 Dec;27(4):541–550. doi: 10.1016/0042-6822(65)90179-0. [DOI] [PubMed] [Google Scholar]
