Mouse Interferon-γ in Liposomes: Pharmacokinetics, Organ-Distribution, and Activation of Spleen and Liver MacrophagesIn Vivo

Abstract

Recombinant mouse interferon-gamma (IFN-gamma) was encapsulated into multilamellar vesicles and the proportion of encapsulated IFN-gamma determined by biological activity was 19%. The distribution of 125I-labeled IFN-gamma liposomes in C57BL/6 mice was analyzed. After an initial enrichment of liposomes in lung, more than 60% of total 125I-labeled IFN-gamma was accumulated in spleen and liver. Furthermore, it was observed if the encapsulation of IFN-gamma in liposomes prevented the rapid decay of IFN-gamma in serum of C57BL/6 mice after intravenous injection. We compared the serum decay curve of liposomal and free IFN-gamma, and showed that IFN-gamma encapsulated in liposomes has an elongated availability in the serum. In addition, we established that a combination of 10(2) U/ml IFN-gamma and 1 microgram/ml MTP-PE, encapsulated in liposomes, activates splenic and starch-elicited peritoneal macrophages in vitro synergistically to kill Leishmania donovani promastigotes. After intravenous injection of liposomal IFN-gamma (5 X 10(3) U) and muramyltripeptide (MTP-PE) (6 micrograms) in C57BL/6 mice, splenic and liver macrophages were activated in vivo to kill Leishmania species in vitro. Neither an injection of the same amount of free substances nor injection of empty liposomes resulted in an increased leishmanicidal activity.

Targeting Dendritic Cells with Antigen-Containing Liposomes

“…In preliminary studies we showed that the incorporation of LPS (1%) into SL can increase their binding to FSDC, suggesting that at least some of the liposome-associated LPS can interact with DC surface receptors, consistent with previous observations (37). In addition, evidence suggests that liposome-associated IFN-␥ is biologically active and that IFN-␥ can be encapsulated within liposomes and as well can bind to the outer surface of liposomes (38,39). Similar findings have been reported with GM-CSF (40).…”

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

“…Other investigators found that incubation of macrophages with IFN-y alone resulted in an increased bactericidal [38,39], antifungal [40,41] and anitiparasitic [42,43] activity. A synergistic antiparasitic activity of macrophages in vitro against Leishmania donovani was shown by Hockertz et al [44] after incubating the macrophages with a combination of MTPPE and IFN-y. Exposure of macrophages in vivo to MTPPE and IFN-y in combination may be realized by injection of liposomes in which both immunomodulators were co-encapsulated.…”

“…They found synergistic effects of MDP and IFN-y in activating macrophages in vitro to tumorcytotoxicity. Hockertz et al [44] found synergistic effects of IFN-y and MTPPE co-encapsulated in liposomes in stimulating the resistance of mice against Leishmania donovani infection.…”

Influence of acetylsalicylic acid on aListeria monocytogenes infection

“…It was shown that interferon gamma production was doubled in the presence of ASA [5]. Interferon gamma increases the antibacterial [19,20] and antiprotozoal defense mechanism against several infections [21,22]. The reports concerning the efficacy of interferon gamma in stimulating host defense mechanisms in L. monocytogenes infection are contradictory [23][24][25][26].…”