Induction of Serum Tumor Necrosis Factor-alpha and Interleukin-6 Activity by Liposome-encapsulated Muramyl Tripeptide-phosphatidylethanolamine (L-MTP-PE) in Normal Cats

Tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6) are products of activated monocytes/ macrophages with anti-tumor activity. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) is a potent monocytelmacrophage activator. Sera from cats after intravenous L-MTP-PE administration showed TNFα activity using a WEHI-164 cell cytotoxicity assay and IL-6 activity using an IL-6 dependent mouse 7TD1 hybridoma cell proliferation assay. Serum TNFα activity peaked at 2 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2 and 3 hours (P<0.05). Neutralization of serum TNFα activity was accomplished with serial dilutions of rhTNFα monoclonal antibody. Serum IL-6 activity peaked at 3 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2, 3, and 4 hours (P<0.05). Neutralization of serum IL-6 activity was not achieved with goat anti-rhIL-6 polyclonal antibody. Intravenous L-MTP-PE, but not lipid-equivalent, induces serum TNFα and IL-6 activity in normal cats.