Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1992 May;60(5):1994–2001. doi: 10.1128/iai.60.5.1994-2001.1992

Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice.

T Katschinski 1, C Galanos 1, A Coumbos 1, M A Freudenberg 1
PMCID: PMC257106  PMID: 1563791

Abstract

Pretreatment of lipopolysaccharide (LPS)-responder C57BL/10ScSn mice with killed Propionibacterium acnes enhanced tumor necrosis factor alpha (TNF-alpha) production and lethality in response to a subsequent challenge with LPS. Sensitization to LPS increased with time of pretreatment and reached its maximum after 7 days. Sensitization was paralleled by gamma interferon (IFN-gamma) production that was detectable from day 3 onward. In contrast, a similar P. acnes pretreatment of LPS-nonresponder C57BL/10ScCr mice had no apparent effect on their high resistance to LPS. Challenge with LPS at any time during the 7-day period after P. acnes treatment led to no detectable TNF-alpha formation and caused no lethal effects. The absence of sensitization in C57BL/10ScCr mice was paralleled by an absence of IFN-gamma production. Administration of monoclonal IFN-gamma antibodies in C57BL/10ScSn mice up to day 3 of P. acnes treatment completely inhibited the overproduction of TNF-alpha by LPS. Anti-IFN-gamma administered later than day 3 had only a partial, although significant, inhibitory effect. Injection of appropriate amounts of anti-IFN-gamma also abolished the development of hypersensitivity to the lethal action of LPS. The effect of exogenously administered IFN-gamma on LPS sensitivity (e.g., TNF-alpha production, lethal effects) was studied in LPS-responder and nonresponder mice. Administration of murine recombinant IFN-gamma increased the sensitivity of C57BL/10ScSn mice to LPS and established LPS responsiveness in LPS-nonresponder C57BL/10ScCr and C3H/HeJ mice. The data provide evidence that IFN-gamma mediates the sensitization towards LPS induced by P. acnes.

Full text

PDF
1994

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berendt M. J., Newborg M. F., North R. J. Increased toxicity of endotoxin for tumor-bearing mice and mice responding to bacterial pathogens: macrophage activation as a common denominator. Infect Immun. 1980 May;28(2):645–647. doi: 10.1128/iai.28.2.645-647.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  3. Beutler B., Tkacenko V., Milsark I., Krochin N., Cerami A. Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype. J Exp Med. 1986 Nov 1;164(5):1791–1796. doi: 10.1084/jem.164.5.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blanchard D. K., Djeu J. Y., Klein T. W., Friedman H., Stewart W. E., 2nd Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages. J Immunol. 1986 Feb 1;136(3):963–970. [PubMed] [Google Scholar]
  5. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chang R. J., Lee S. H. Effects of interferon-gamma and tumor necrosis factor-alpha on the expression of an Ia antigen on a murine macrophage cell line. J Immunol. 1986 Nov 1;137(9):2853–2856. [PubMed] [Google Scholar]
  7. Clark I. A. Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis? Lancet. 1978 Jul 8;2(8080):75–77. doi: 10.1016/s0140-6736(78)91386-7. [DOI] [PubMed] [Google Scholar]
  8. Collart M. A., Belin D., Vassalli J. D., de Kossodo S., Vassalli P. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med. 1986 Dec 1;164(6):2113–2118. doi: 10.1084/jem.164.6.2113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Danis V. A., Franic G. M., Rathjen D. A., Brooks P. M. Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 on the production of immunoreactive IL-1 and TNF-alpha by human monocytes. Clin Exp Immunol. 1991 Jul;85(1):143–150. doi: 10.1111/j.1365-2249.1991.tb05695.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Djeu J. Y., Stocks N., Zoon K., Stanton G. J., Timonen T., Herberman R. B. Positive self regulation of cytotoxicity in human natural killer cells by production of interferon upon exposure to influenza and herpes viruses. J Exp Med. 1982 Oct 1;156(4):1222–1234. doi: 10.1084/jem.156.4.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Esparza I., Männel D., Ruppel A., Falk W., Krammer P. H. Interferon gamma and lymphotoxin or tumor necrosis factor act synergistically to induce macrophage killing of tumor cells and schistosomula of Schistosoma mansoni. J Exp Med. 1987 Aug 1;166(2):589–594. doi: 10.1084/jem.166.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fertsch D., Vogel S. N. Recombinant interferons increase macrophage Fc receptor capacity. J Immunol. 1984 May;132(5):2436–2439. [PubMed] [Google Scholar]
  13. Fomsgaard A., Freudenberg M. A., Bendtzen K., Galanos C. Quantitation and biological activities of native tumour necrosis factor from LPS-stimulated human monocytes. APMIS. 1990 Jun;98(6):529–534. doi: 10.1111/j.1699-0463.1990.tb01067.x. [DOI] [PubMed] [Google Scholar]
  14. Freudenberg M. A., Galanos C. Induction of tolerance to lipopolysaccharide (LPS)-D-galactosamine lethality by pretreatment with LPS is mediated by macrophages. Infect Immun. 1988 May;56(5):1352–1357. doi: 10.1128/iai.56.5.1352-1357.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Freudenberg M. A., Galanos C. Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. Infect Immun. 1991 Jun;59(6):2110–2115. doi: 10.1128/iai.59.6.2110-2115.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Freudenberg M. A., Keppler D., Galanos C. Requirement for lipopolysaccharide-responsive macrophages in galactosamine-induced sensitization to endotoxin. Infect Immun. 1986 Mar;51(3):891–895. doi: 10.1128/iai.51.3.891-895.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Freudenberg M. A., Kumazawa Y., Meding S., Langhorne J., Galanos C. Gamma interferon production in endotoxin-responder and -nonresponder mice during infection. Infect Immun. 1991 Oct;59(10):3484–3491. doi: 10.1128/iai.59.10.3484-3491.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Galanos C., Freudenberg M. A., Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5939–5943. doi: 10.1073/pnas.76.11.5939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Galanos C., Lüderitz O., Westphal O. Preparation and properties of a standardized lipopolysaccharide from salmonella abortus equi (Novo-Pyrexal). Zentralbl Bakteriol Orig A. 1979 Apr;243(2-3):226–244. [PubMed] [Google Scholar]
  20. Gifford G. E., Lohmann-Matthes M. L. Gamma interferon priming of mouse and human macrophages for induction of tumor necrosis factor production by bacterial lipopolysaccharide. J Natl Cancer Inst. 1987 Jan;78(1):121–124. doi: 10.1093/jnci/78.1.121. [DOI] [PubMed] [Google Scholar]
  21. Green S., Dobrjansky A., Chiasson M. A., Carswell E., Schwartz M. K., Old L. J. Corynebacterium parvum as the priming agent in the production of tumor necrosis factor in the mouse. J Natl Cancer Inst. 1977 Nov;59(5):1519–1522. doi: 10.1093/jnci/59.5.1519. [DOI] [PubMed] [Google Scholar]
  22. HALPERN B. N., PREVOT A. R., BIOZZI G., STIFFEL C., MOUTON D., MORARD J. C., BOUTHILLIER Y., DECREUSEFOND C. STIMULATION DE L'ACTIVIT'E PHAGOCYTAIRE DU SYST'EME R'ETICULOENDOTH'ELIAL PROVOQU'EE PAR CORYNEBACTERIUM PARVUM. J Reticuloendothel Soc. 1964 Jan;1:77–96. [PubMed] [Google Scholar]
  23. Handa K., Suzuki R., Matsui H., Shimizu Y., Kumagai K. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). II. IL 2-induced interferon gamma production. J Immunol. 1983 Feb;130(2):988–992. [PubMed] [Google Scholar]
  24. Heinzel F. P. The role of IFN-gamma in the pathology of experimental endotoxemia. J Immunol. 1990 Nov 1;145(9):2920–2924. [PubMed] [Google Scholar]
  25. Heremans H., Van Damme J., Dillen C., Dijkmans R., Billiau A. Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice. J Exp Med. 1990 Jun 1;171(6):1853–1869. doi: 10.1084/jem.171.6.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hogan M. M., Vogel S. N. Production of tumor necrosis factor by rIFN-gamma-primed C3H/HeJ (Lpsd) macrophages requires the presence of lipid A-associated proteins. J Immunol. 1988 Dec 15;141(12):4196–4202. [PubMed] [Google Scholar]
  27. Johnson H. M., Stanton G. J., Baron S. Relative ability of mitogens to stimulate production of interferon by lymphoid cells and to induce suppression of the in vitro immune response. Proc Soc Exp Biol Med. 1977 Jan;154(1):138–141. [PubMed] [Google Scholar]
  28. Jupin C., Anderson S., Damais C., Alouf J. E., Parant M. Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon. J Exp Med. 1988 Mar 1;167(3):752–761. doi: 10.1084/jem.167.3.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kagaya K., Watanabe K., Fukazawa Y. Capacity of recombinant gamma interferon to activate macrophages for Salmonella-killing activity. Infect Immun. 1989 Feb;57(2):609–615. doi: 10.1128/iai.57.2.609-615.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  31. Le J., Lin J. X., Henriksen-DeStefano D., Vilcek J. Bacterial lipopolysaccharide-induced interferon-gamma production: roles of interleukin 1 and interleukin 2. J Immunol. 1986 Jun 15;136(12):4525–4530. [PubMed] [Google Scholar]
  32. Lehmann V., Freudenberg M. A., Galanos C. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med. 1987 Mar 1;165(3):657–663. doi: 10.1084/jem.165.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Liem H. H., Cardenas F., Tavassoli M., Poh-Fitzpatrick M. B., Muller-Eberhard U. Quantitative determination of hemoglobin and cytochemical staining for peroxidase using 3,3',5,5'-tetramethylbenzidine dihydrochloride, a safe substitute for benzidine. Anal Biochem. 1979 Oct 1;98(2):388–393. doi: 10.1016/0003-2697(79)90157-x. [DOI] [PubMed] [Google Scholar]
  34. Luedke C. E., Cerami A. Interferon-gamma overcomes glucocorticoid suppression of cachectin/tumor necrosis factor biosynthesis by murine macrophages. J Clin Invest. 1990 Oct;86(4):1234–1240. doi: 10.1172/JCI114829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Marcucci F., Waller M., Kirchner H., Krammer P. Production of immune interferon by murine T-cell clones from long-term cultures. Nature. 1981 May 7;291(5810):79–81. doi: 10.1038/291079a0. [DOI] [PubMed] [Google Scholar]
  36. Matsumura H., Nakano M. Endotoxin-induced interferon-gamma production in culture cells derived from BCG-infected C3H/HeJ mice. J Immunol. 1988 Jan 15;140(2):494–500. [PubMed] [Google Scholar]
  37. Michalek S. M., Moore R. N., McGhee J. R., Rosenstreich D. L., Mergenhagen S. E. The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxim. J Infect Dis. 1980 Jan;141(1):55–63. doi: 10.1093/infdis/141.1.55. [DOI] [PubMed] [Google Scholar]
  38. Michie H. R., Manogue K. R., Spriggs D. R., Revhaug A., O'Dwyer S., Dinarello C. A., Cerami A., Wolff S. M., Wilmore D. W. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med. 1988 Jun 9;318(23):1481–1486. doi: 10.1056/NEJM198806093182301. [DOI] [PubMed] [Google Scholar]
  39. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Nathan I., Groopman J. E., Quan S. G., Bersch N., Golde D. W. Immune (gamma) interferon produced by a human T-lymphoblast cell line. Nature. 1981 Aug 27;292(5826):842–844. doi: 10.1038/292842a0. [DOI] [PubMed] [Google Scholar]
  41. O'Garra A. Interleukins and the immune system 2. Lancet. 1989 May 6;1(8645):1003–1005. doi: 10.1016/s0140-6736(89)92640-8. [DOI] [PubMed] [Google Scholar]
  42. Pace J. L., Russell S. W., Torres B. A., Johnson H. M., Gray P. W. Recombinant mouse gamma interferon induces the priming step in macrophage activation for tumor cell killing. J Immunol. 1983 May;130(5):2011–2013. [PubMed] [Google Scholar]
  43. Prat M., Gribaudo G., Comoglio P. M., Cavallo G., Landolfo S. Monoclonal antibodies against murine gamma interferon. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4515–4519. doi: 10.1073/pnas.81.14.4515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. SUTER E., ULLMAN G. E., HOFFMAN R. G. Sensitivity of mice to endotoxin after vaccination with BCG (Bacillus Calmette-Guérin). Proc Soc Exp Biol Med. 1958 Oct;99(1):167–169. doi: 10.3181/00379727-99-24282. [DOI] [PubMed] [Google Scholar]
  45. Salvin S. B., Youngner J. S., Lederer W. H. Migration inhibitory factor and interferon in the circulation of mice with delayed hypersensitivity. Infect Immun. 1973 Jan;7(1):68–75. doi: 10.1128/iai.7.1.68-75.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Schramek S., Kazar J., Sekeyova Z., Freudenberg M. A., Galanos C. Induction of hyperreactivity to endotoxin in mice by Coxiella burnetii. Infect Immun. 1984 Sep;45(3):713–717. doi: 10.1128/iai.45.3.713-717.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Slade S. J., Langhorne J. Production of interferon-gamma during infection of mice with Plasmodium chabaudi chabaudi. Immunobiology. 1989 Oct;179(4-5):353–365. doi: 10.1016/S0171-2985(89)80041-5. [DOI] [PubMed] [Google Scholar]
  48. Spitalny G. L., Havell E. A. Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. J Exp Med. 1984 May 1;159(5):1560–1565. doi: 10.1084/jem.159.5.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Tanamoto K., Galanos C., Lüderitz O., Kusumoto S., Shiba T. Mitogenic activities of synthetic lipid A analogs and suppression of mitogenicity of lipid A. Infect Immun. 1984 May;44(2):427–433. doi: 10.1128/iai.44.2.427-433.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tanamoto K., Zähringer U., McKenzie G. R., Galanos C., Rietschel E. T., Lüderitz O., Kusumoto S., Shiba T. Biological activities of synthetic lipid A analogs: pyrogenicity, lethal toxicity, anticomplement activity, and induction of gelation of Limulus amoebocyte lysate. Infect Immun. 1984 May;44(2):421–426. doi: 10.1128/iai.44.2.421-426.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  52. Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  53. Vogel S. N., Hansen C. T., Rosenstreich D. L. Characterization of a congenitally LPS-resistant, athymic mouse strain. J Immunol. 1979 Feb;122(2):619–622. [PubMed] [Google Scholar]
  54. Vogel S. N., Moore R. N., Sipe J. D., Rosenstreich D. L. BCG-induced enhancement of endotoxin sensitivity in C3H/HeJ mice. I. In vivo studies. J Immunol. 1980 Apr;124(4):2004–2009. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES