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British Journal of Experimental Pathology logoLink to British Journal of Experimental Pathology
. 1986 Aug;67(4):587–596.

Recombinant interferon-gamma and chemotherapy with isoniazid and rifampicin in experimental murine tuberculosis.

M Khor, D B Lowrie, A R Coates, D A Mitchison
PMCID: PMC2013056  PMID: 3091058

Abstract

Viable bacterial counts in the lungs and spleens of mice infected intravenously with Mycobacterium tuberculosis, strain H37Rv were reduced by intravenous recombinant murine interferon-gamma (IFN-gamma) 1000-5000 u, but not by 200 u. Reduction in counts was greatest when IFN-gamma was given 1 day before infection and was not increased by additional doses in the preceding 2 days. The effect was complete in 1 day and was not increased by successive doses during the next week. Giving IFN-gamma in multilamellar liposomes further reduced the spleen viable counts, but this appeared due to the liposomes themselves and not to encapsulation of IFN-gamma within them. Only a minimal reduction in organ viable counts, not statistically significant, occurred when IFN-gamma was given 5 days after infection. Although IFN-gamma alone and isoniazid 25 mg/kg alone reduced the organ viable counts, combined treatment with IFN-gamma and isoniazid was no more bactericidal than isoniazid alone. Similarly, the bactericidal activity of rifampicin 25 mg/kg was not increased by simultaneous administration of IFN-gamma. There seems little likelihood that IFN-gamma would increase the efficacy of the early stages of the chemotherapy of tuberculosis.

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Selected References

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

  1. Banerjee D. K., Sharp A. K., Lowrie D. B. The effect of gamma-interferon during Mycobacterium bovis (BCG) infection in athymic and euthymic mice. Microb Pathog. 1986 Apr;1(2):221–224. doi: 10.1016/0882-4010(86)90024-0. [DOI] [PubMed] [Google Scholar]
  2. Baron S., Howie V., Langford M., Macdonald E. M., Stanton G. J., Reitmeyer J., Weigent D. A. Induction of interferon by bacteria, protozoa, and viruses: defensive role. Tex Rep Biol Med. 1981;41:150–157. [PubMed] [Google Scholar]
  3. Fidler I. J., Barnes Z., Fogler W. E., Kirsh R., Bugelski P., Poste G. Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators. Cancer Res. 1982 Feb;42(2):496–501. [PubMed] [Google Scholar]
  4. Fidler I. J. Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines. Science. 1980 Jun 27;208(4451):1469–1471. doi: 10.1126/science.7384789. [DOI] [PubMed] [Google Scholar]
  5. Fleischmann W. R., Jr, Kleyn K. M., Baron S. Potentiation of antitumor effect of virus-induced interferon by mouse immune interferon preparations. J Natl Cancer Inst. 1980 Nov;65(5):963–966. [PubMed] [Google Scholar]
  6. Fraser-Smith E. B., Eppstein D. A., Larsen M. A., Matthews T. R. Protective effect of a muramyl dipeptide analog encapsulated in or mixed with liposomes against Candida albicans infection. Infect Immun. 1983 Jan;39(1):172–178. doi: 10.1128/iai.39.1.172-178.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gray D. F., Cheers C. The steady state in cellular immunity. I. Chemotherapy and superinfection in murine tuberculosis. Aust J Exp Biol Med Sci. 1967 Aug;45(4):407–416. doi: 10.1038/icb.1967.39. [DOI] [PubMed] [Google Scholar]
  8. Gray P. W., Goeddel D. V. Cloning and expression of murine immune interferon cDNA. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5842–5846. doi: 10.1073/pnas.80.19.5842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gray P. W., Leung D. W., Pennica D., Yelverton E., Najarian R., Simonsen C. C., Derynck R., Sherwood P. J., Wallace D. M., Berger S. L. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
  10. Izadkhah Z., Mandel A. D., Sonnenfeld G. Effect of treatment of mice with sera containing gamma interferon on the course of infection with Salmonella typhimurium strain LT-2. J Interferon Res. 1980 Fall;1(1):137–145. doi: 10.1089/jir.1980.1.137. [DOI] [PubMed] [Google Scholar]
  11. Kim T. H., Kubica G. P. Preservation of mycobacteria: 100 percent viability of suspensions stored at -70 C. Appl Microbiol. 1973 Jun;25(6):956–960. doi: 10.1128/am.25.6.956-960.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koff W. C., Showalter S. D., Hampar B., Fidler I. J. Protection of mice against fatal herpes simplex type 2 infection by liposomes containing muramyl tripeptide. Science. 1985 Apr 26;228(4698):495–497. doi: 10.1126/science.2984772. [DOI] [PubMed] [Google Scholar]
  13. Mitchison D. A., Allen B. W., Carrol L., Dickinson J. M., Aber V. R. A selective oleic acid albumin agar medium for tubercle bacilli. J Med Microbiol. 1972 May;5(2):165–175. doi: 10.1099/00222615-5-2-165. [DOI] [PubMed] [Google Scholar]
  14. PIERCE C. H., DUBOS R. J., SCHAEFER W. B. Multiplication and survival of tubercle bacilli in the organs of mice. J Exp Med. 1953 Feb 1;97(2):189–206. doi: 10.1084/jem.97.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Phillips N. C., Moras M. L., Chedid L., Lefrancier P., Bernard J. M. Activation of alveolar macrophage tumoricidal activity and eradication of experimental metastases by freeze-dried liposomes containing a new lipophilic muramyl dipeptide derivative. Cancer Res. 1985 Jan;45(1):128–134. [PubMed] [Google Scholar]
  16. Preble O. T., Friedman R. M. Interferon-induced alterations in cells: relevance to viral and nonviral diseases. Lab Invest. 1983 Jul;49(1):4–18. [PubMed] [Google Scholar]
  17. REES R. J., HART P. D. Analysis of the host-parasite equilibrium in chronic murine tuberculosis by total and viable bacillary counts. Br J Exp Pathol. 1961 Feb;42:83–88. [PMC free article] [PubMed] [Google Scholar]
  18. Sone S., Fidler I. J. In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes. Cell Immunol. 1981 Jan 1;57(1):42–50. doi: 10.1016/0008-8749(81)90118-0. [DOI] [PubMed] [Google Scholar]

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