Effect of Adriamycin on liposomal muramyl tripeptide's ability to up-regulate monocyte cytokine expression

Autor: Amanda McWatters, Takeshi Asano, Taeha An, Eugenie S. Kleinerman, Kouji Matsushima, Wakae Fujimaki
Rok vydání: 1993
Předmět:
Zdroj: Cancer Immunology Immunotherapy. 37:408-411
ISSN: 1432-0851
0340-7004
DOI: 10.1007/bf01526798
Popis: 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.
Databáze: OpenAIRE