Systemic activation of tumoricidal properties in mouse macrophages and inhibition of melanoma metastases by the oral administration of MTP-PE, a lipophilic muramyl dipeptide.

Abstract

The purpose of these studies was to determine whether the oral administration of a lipophilic analog of muramyl dipeptide, MTP-PE, can produce in situ activation of tumoricidal properties in mouse macrophages. MTP-PE was dissolved in a phosphate-buffered saline to produce micelles. Single or multiple oral administrations of MTP-PE produced tumoricidal activation in both lung and peritoneal macrophages. This was in direct contrast to the i.v. or i.p. administrations of MTP-PE incorporated in liposomes, which produced activation in only lung or only peritoneal macrophages, respectively. The distribution and fate of [3H]-labeled MTP-PE subsequent to oral administration revealed that MTP-PE was found in various organs independent of reticuloendothelial activity. Finally, the repeated twice-weekly oral administrations of MTP-PE inhibited lung and lymph node metastasis in C57BL/6 mice by syngeneic B16 melanoma cells. The oral administration of MTP-PE, however, was not effective in eradicating well-established melanoma metastases. We conclude that the oral administration of a lipophilic muramyl dipeptide produces systemic activation of macrophages. The feasibility of enhancing host defense against infections and cancer by the oral administration of an immunomodulator has obvious clinical advantages.

• Authors: I J Fidler, W E Fogler, A F Brownbill, G Schumann
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 138 Issue 12 Pg. 4509-14 (Jun 15 1987) ISSN: 0022-1767 [Print] United States
• PMID: 3584979 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Liposomes
• Phosphatidylethanolamines
• mifamurtide
• Acetylmuramyl-Alanyl-Isoglutamine
• N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine

Topics

• Acetylmuramyl-Alanyl-Isoglutamine (administration & dosage, analogs & derivatives, metabolism, pharmacology, therapeutic use)
• Administration, Oral
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology, therapeutic use)
• Female
• Liposomes
• Lung (pathology)
• Lung Neoplasms (drug therapy, secondary)
• Lymphatic Metastasis (drug therapy)
• Macrophage Activation (drug effects)
• Macrophages (drug effects, physiology)
• Melanoma (drug therapy, secondary)
• Mice
• Mice, Inbred Strains
• Peritoneal Cavity (pathology)
• Phosphatidylethanolamines (administration & dosage, pharmacology, therapeutic use)
• Tissue Distribution