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 (TNFalpha) and interleukin-6 (IL-6) are pr oducts of activated monocytes/macrophages with anti-tumor activity. Li posome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP -PE) is a potent monocyte/macrophage activator. Sera from cats after i ntravenous L-MTP-PE administration showed TNFalpha activity using a WE HI-164 cell cytotoxicity assay and IL-6 activity using an IL-6 depende nt mouse 7TD1 hybridoma cell proliferation assay. Serum TNFalpha activ ity peaked at 2 hours after L-MTP-PE administration. Significant diffe rences from lipid-equivalent controls were observed at 2 and 3 hours ( P <0.05). Neutralization of serum TNFalpha activity was accomplished w ith serial dilutions of rhTNFalpha monoclonal antibody. Serum IL-6 act ivity peaked at 3 hours after L-MTP-PE administration. Significant dif ferences from lipid-equivalent controls were observed at 2, 3, and 4 h ours (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 TNFalpha and IL-6 activity in norm al cats.