EFFECT OF LIPOSOME-MURAMYL TRIPEPTIDE COMBINED WITH RECOMBINANT CANINE GRANULOCYTE-COLONY-STIMULATING FACTOR ON CANINE MONOCYTE ACTIVITY

Liposome-muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) has be en shown to activate monocytes in vivo to become tumoricidal resulting in reduction in metastasis as well as prolongation of survival time i n murine and canine tumor models. Granulocyte colony-stimulating facto r (G-CSF) is a cytokine which will stimulate the proliferation of gran ulocytes as well as monocytes. Recombinant canine G-CSF (rcG-CSF) was administered to normal dogs as a method of increasing the monocyte pop ulation prior to in vivo monocyte activation using L-MTP-PE. rcG-CSF a dministration resulted in a 3.5-fold increase in absolute monocyte cou nts and when combined with L-MTP-PE, resulted in an enhanced level of serum tumor necrosis factor-alpha activity compared to dogs treated wi th L-MTP-PE alone. G-CSF alone did not affect monocyte cytostatic acti vity, however, dogs receiving G-CSF had a significant increase in mono cyte cytostatic activity following L-MTP-PE. The combined use of CSFs and effector cell activators deserves further evaluation in clinical t rials.