Effect of Adriamycin on liposomal muramyl tripeptide's 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 melanoma. 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 ultimate goal is to combine L-MTP-PE with chemotherapy. The purpose of this 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 Adriamycin for 3 h and washed before being exposed to 2 micrograms/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 up-regulation of any of these cytokines. We concluded that combination therapy with L-MTP-PE and Adriamycin is feasible and that this combination warrants further investigation in a clinical setting.
Asano
T
T
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Fujimaki
W
W
McWatters
A
A
An
T
T
Matsushima
K
K
Kleinerman
E S
ES
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers; D004347:Drug Interactions; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008081:Liposomes; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D000199:Actins; D000970:Antineoplastic Agents; D016207:Cytokines; D004337:Drug Carriers; D007378:Interleukins; D008081:Liposomes; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D004317:Doxorubicin