Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance

Background. Immune status of the liver may affect growth of liver metastase s. We analyzed the ability of muramyl tripeptide phosphatidylethanolamine ( MTP-PE) an immunomodulatory bacterial cell wall analog, to stimulate Kupffe r cells (KCs) and protect against tumor growth, with or without an immunosu ppressive partial hepatectomy (PH). Impact of MTP-PE's route of administrat ion on KC function was assessed. Methods. Buffalo rats (n = 7 to 12/group) were treated with saline, 40 mu g 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 im pact 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 animal s (19 vs 184, P < .005). MTP-PE-portal animals had fewer nodules than MTP-P E-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 admini stration 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 microscopi c tumor cells. MTP-PE's effects persist after an immunosuppressive hepatect omy. Portal administration was the most effective. MTP-PE administration ma y be useful as a neoadjuvant therapy for patients undergoing resection of l iver malignancies.