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Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor
H M Karpoff1, W Jarnagin, K Delman
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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.