Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance.
BACKGROUND
Immune status of the liver may affect growth of liver metastases. We analyzed the ability of muramyl tripeptide phosphatidylethanolamine (MTP-PE), an immunomodulatory bacterial cell wall analog, to stimulate Kupffer cells (KCs) and protect against tumor growth, with or without an immunosuppressive partial hepatectomy (PH). Impact of MTP-PE's route of administration on KC function was assessed.


METHODS
Buffalo rats (n = 7 to 12/group) were treated with saline, 40 microg MTP-PE intraportally (portal) or intravenously (IV) and challenged with 5 x 10(5) hepatoma cells, and tumors counted on day 21. To assess MTP-PE's impact on KC stimulation in animals undergoing PH, a known stimulant of tumor cell growth, groups were treated with saline or MTP-PE and challenged with tumor and underwent 30% PH. KCs were harvested and analyzed for superoxide production. Statistical analysis was performed with Mann-Whitney U test or chi-square test.


RESULTS
MTP-PE-treated animals had fewer tumor nodules than control animals (19 vs 184, P <.005). MTP-PE-portal animals had fewer nodules than MTP-PE-IV (2 vs 36, P <.05). MTP-PE treatment before PH resulted in fewer tumor nodules compared with control animals (192 vs 276, P <. 05). MTP-PE administration increased macrophage superoxide production (20.6 +/- 2 vs 11.9 +/- 1.1 nmol/10(6) cells, P <.005).


CONCLUSIONS
MTP-PE improved KC function and decreased growth of microscopic tumor cells. MTP-PE's effects persist after an immunosuppressive hepatectomy. Portal administration was the most effective. MTP-PE administration may be useful as a neoadjuvant therapy for patients undergoing resection of liver malignancies.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
H M
HM
Karpoff
W
W
Jarnagin
K
K
Delman
Y
Y
Fong
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004337:Drug Carriers; D006498:Hepatectomy; D007262:Infusions, Intravenous; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology*; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011168:Portal System; D051381:Rats; D011915:Rats, Inbred BUF; D013481:Superoxides / Q000378:metabolism
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D013481:Superoxides; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine