EFFECT OF ADRIAMYCIN ON LIPOSOMAL MURAMYL TRIPEPTIDES ABILITY TO UP-REGULATE MONOCYTE CYTOKINE EXPRESSION

Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a biological agent in phase I and II trials for osteosarcoma and melanom a. Its mechanism of action has been linked to its ability to activate monocyte tumoricidal function and to stimulate monocyte production of tumor necrosis factor (TNF) and interleukins(IL)-1, -6, and -8. Our ul timate goal is to combine L-MTP-PE with chemotherapy. The purpose of t his study was to determine whether doxorubicin (Adriamycin) interfered with the ability of L-MTP-PE to activate monocyte cytokine production . Human monocytes were cultured with or without 5-500 ng/ml of Adriamy cin for 3 h and washed before being exposed to 2 mu g/ml L-MTP-PE for 16 h. Cultured supernatants were collected and assayed for TNF, IL-1, IL-6, and IL-8. The messenger RNA expression of IL-1 alpha, IL-1 beta, TNF alpha, IL-6, and IL-8 was quantified with northern blot analysis. Adriamycin did not suppress the upregulation of any of these cytokine s. We concluded that combination therapy with L-MTP-PE and Adriamycin is feasible and that this combination warrents further investigation i n a clinical setting.