Biotherapy

, Volume 6, Issue 2, pp 113–124 | Cite as

Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) in experimental infection with Listeria Monocytogenes

  • P. M. B. Melissen
  • W. van Vianen
  • O. Bidjai
  • M. van Marion
  • I. A. J. M. Bakker-Woudenberg
Research Articles

Abstract

The effect of free and liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) on the resistance againstListeria monocytogenes infection in mice was investigated. It was shown that administration of MTPPE or IFN-y at 24 h before bacterial inoculation led to increased resistance againstL. monocytogenes infection in terms of a decrease in bacterial numbers in liver and spleen. Encapsulation of MTPPE and IFN-y in liposomes increased their efficacy 33- or 66-fold, respectively. In addition, liposomal encapsulation led to a more rapid decrease in bacterial numbers. The immunomodulator to lipid ratio appeared to be very important in the antibacterial effect of LE-MTPPE and LE-IFN-y. When nontherapeutic doses of liposome-encapsulated MTPPE or IFN-y were administered in a larger amount of lipid (so at higher lipid: immunomodulator ratio), these doses became effective. Exposure of macrophages in monolayer infected withL. monocytogenes in vitro to MTPPE had no effect, whereas exposure to IFN-y only led to growth inhibition of the intracellular bacteria. However, incubation of macrophages with a combination of MTPPE and IFN-y resulted in killing of the intracellular bacteria. Exposure of macrophages in vivo to both immunomodulators in combination can be effected by using liposomes as carriers. It was observed that administration of MTPPE and IFN-y co-encapsulated in liposomes resulted in a synergistic enhanced antibacterial resistance againstL. monocytogenes. Both reactive oxygen and nitrogen intermediates seemed to play a role in the killing ofL. monocytogenes by macrophages activated with a combination of MTPPE and IFN-y.

Key words

IFN-y liposomes Listeria macrophages muramyl tripeptide (MTPPE) 

Abbreviations

MTPPE

muramyl tripeptide phosphatidylethanolamide

IFN-y

interferon-y

LE-MTPPE

liposome-encapsulated MTPPE

LE-IFN-y

liposome-encapsulated IFN-y

MPS

mononuclear phagocyte system

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Copyright information

© Kluwer Academic Publishers 1993

Authors and Affiliations

  • P. M. B. Melissen
    • 1
  • W. van Vianen
    • 1
  • O. Bidjai
    • 1
  • M. van Marion
    • 1
  • I. A. J. M. Bakker-Woudenberg
    • 1
  1. 1.Dept. Clinical Microbiology and Antimicrobial TherapyErasmus University RotterdamDR RotterdamThe Netherlands

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