title: Synergism of recombinant human interferon gamma with liposome-encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes.
abstract: Freshly isolated human peripheral blood monocytes from healthy volunteers are not cytotoxic to allogeneic A375 melanoma cells, but they were rendered tumoricidal by incubation in vitro with either liposomes containing 5 micrograms/mumol phospholipid of muramyl tripeptide phosphatidylethanolamine (liposome-MTP-PE; optimal dose, 500 nmol/ml) or recombinant human interferon gamma (rIFN-gamma; optimal dose, 100 U/ml). A combination of sub-threshold concentrations of liposome-MTP-PE (50 nmol/ml) and rIFN-gamma (1 or 10 U/ml) also induced significant tumor-cell killing, indicating that the effects of rIFN-gamma and liposome-MTP-PE in monocyte activation are synergistic. In contrast to rIFN-gamma, recombinant IFN-alpha and IFN-beta had additive effects with liposome-MTP-PE in human monocyte activation. Since recombinant human IFN-gamma has a synergistic effect with liposome-MTP-PE in monocyte activation, unlike IFN-alpha or IFN-beta, and liposome-MTP-PE as well as rIFN-gamma is available at standardized concentrations, this combination could be of clinical value in the treatment of disseminated malignant disease.
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects; D008545:Melanoma; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D008081:Liposomes; D011994:Recombinant Proteins; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C035104:muramylNAc-Ala-isoGln-Lys-tripeptide; D007371:Interferon-gamma