FREE VERSUS LIPOSOME-ENCAPSULATED MURAMYL TRIPEPTIDE PHOSPHATIDYLETHANOLAMIDE (MTPPE) AND INTERFERON-Y (IFN-Y) IN EXPERIMENTAL-INFECTION WITH LISTERIA-MONOCYTOGENES

The effect of free and liposome-encapsulated muramyl tripeptide phosph atidylethanolamide (MTPPE) and interferon-gamma (IFN-gamma) on the res istance against Listeria monocytogenes infection in mice was investiga ted. It was shown that administration of MTPPE or IFN-gamma at 24 h be fore bacterial inoculation led to increased resistance against L. mono cytogenes infection in terms of a decrease in bacterial numbers in liv er and spleen. Encapsulation of MTPPE and IFN-gamma in liposomes incre ased their efficacy 33- or 66-fold, respectively. In addition, liposom al encapsulation led to a more rapid decrease in bacterial numbers. Th e immunomodulator to lipid ratio appeared to be very important in the antibacterial effect of LE-MTPPE and LE-IFN-gamma. When nontherapeutic doses of liposome-encapsulated MTPPE or IFN-gamma were administered i n a larger amount of lipid (so at higher lipid: immunomodulator ratio) , these doses became effective. Exposure of macrophages in monolayer i nfected with L. monocytogenes in vitro to MTPPE had no effect, whereas exposure to IFN-gamma only led to growth inhibition of the intracellu lar bacteria. However, incubation of macrophages with a combination of MTPPE and IFN-gamma resulted in killing of the intracellular bacteria . Exposure of macrophages in vivo to both immunomodulators in combinat ion can be effected by using liposomes as carriers. It was observed th at administration of MTPPE and IFN-gamma 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 acti vated with a combination of MTPPE and IFN-gamma.