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 been shown to activate monocytes in vivo to become tumoricidal resulting in reduction in metastasis as well as prolongation of survival time in murine and canine tumor models. Granulocyte colony-stimulating factor (G-CSF) is a cytokine which will stimulate the proliferation of granulocytes as well as monocytes. Recombinant canine G-CSF (rcG-CSF) was administered to normal dogs as a method of increasing the monocyte population prior to in vivo monocyte activation using L-MTP-PE. rcG-CSF administration resulted in a 3.5-fold increase in absolute monocyte counts and when combined with L-MTP-PE, resulted in an enhanced level of serum tumor necrosis factor-α activity compared to dogs treated with L-MTP-PE alone. G-CSF alone did not affect monocyte cytostatic activity, however, dogs receiving G-CSF had a significant increase in monocyte cytostatic activity following L-MTP-PE. The combined use of CSFs and effector cell activators deserves further evaluation in clinical trials.