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

Abstract

The effect of free and liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) on the resistance against Listeria 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 against L. 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 with L. 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 against L. monocytogenes. Both reactive oxygen and nitrogen intermediates seemed to play a role in the killing of L. monocytogenes by macrophages activated with a combination of MTPPE and IFN-y.

Effects of Muramyl Peptides on Macrophages, Monokines, and Sleep

“…Administration of muramyl peptides cures lethal infections by bacteria, fungi, and parasites. These cures have been obtained with MDP in animal models given lethal infections with Klebsiella pneumoniae [20,100], Listeria monocytogenes [101], C. albicans [21], Trypanosoma cruzi [102,103], and Schistosoma mansoni [104]. Protection of mice from a lethal infection with C. albicans is shown in figure 7.…”

Imunomodulative effect of liposomized muramyltripeptide phosphatidylethanolamine (L-MTP-PE) on mice with alveolar echinococcosis and treated with albendazole

“…Tanguay et al (1994) found that L-MTP-PE administered alone activated peritoneal macrophages with lower intensity, but co-incubation of macrophages with L-MTP-PE and IFN-γ together has duplicated their cytotoxicity. An important role of IFN-γ in effect of the immunomodulator on macrophages infected with Listeria monocytogenes was also verified by Melissen et al (1993b). Ten Hagen et al (1998) underlined IFN-γ contribution to immunomodulative effect of L-MTP-PE in Klebsiella pneumoniae infection of mice and thus confirmed a key role of T cells in immunity boost of immunomodulated host organism.…”

Liposomes as delivery systems in the prevention and treatment of infectious diseases

“…As liposome-encapsuJated immunomodulators exert their action mainly via fixed macrophages, the first studies in this field were performed in intracellular infections of the cells of the MPS. It was demonstrated that liposome-encapsulated IFN 7 was more effective than the free agent in animal models of infection caused by Listeria monocytogenes [65] and Leishmania donovani [64]. These micro-organisms replicate primarily inside macrophages of the MPS.…”

“…This may be accomplished by the administration of the immunomodulators co-encapsulated in the same liposome, which will result in simultaneous delivery of the agents to the target cell. Treatment of Listeria infection with MTP-PE and IFN T in the same liposome resulted in an enhanced antimicrobial resistance [65]. Synergism between liposomal MTP-PE and IFNTwas also shown in a Leishmania infection model [64] and in tumour models [70].…”