Liposomal muramyl tripeptide up-regulates interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 gene expression in human monocytes.

Abstract

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a new biologic agent presently in clinical trials for metastatic osteosarcoma and melanoma. The mechanism of L-MTP-PE antitumor activity is linked to its activation of monocyte tumoricidal function. The purpose of this study was to determine whether L-MTP-PE affected the expression of cytokine genes in monocytes. Monocyte interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha expression were all up-regulated after a 2-h incubation with L-MTP-PE. The increased expression of IL-1 alpha, IL-1 beta, IL-6 and IL-8 persisted up to 72 h. Increased TNF-alpha expression declined by 24 h. The kinetics of cytokine expression stimulated by L-MTP-PE were different from those seen after lipopolysaccharide (LPS) stimulation. Lipopolysaccharide stimulation caused a rapid increase in cytokine expression followed by a rapid decline. L-MTP-PE did not affect the expression of these cytokines in lymphocytes, nor did L-MTP-PE upregulate IL-2 expression in lymphocytes. The early up-regulation of all five cytokines was due to an increase in the transcriptional activity. Modification of mRNA stability was not detected at 2 h but was seen after a 24-h exposure to L-MTP-PE. The subsequent production and secretion of these cytokine proteins may play a role in L-MTP-PE antitumor activity.

• Authors: T Asano, A McWatters, T An, K Matsushima, E S Kleinerman
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 268 Issue 2 Pg. 1032-9 (Feb 1994) ISSN: 0022-3565 [Print] United States
• PMID: 8113959 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Cytokines
• Interleukin-1
• Interleukin-6
• Interleukin-8
• Liposomes
• Phosphatidylethanolamines
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• mifamurtide
• Acetylmuramyl-Alanyl-Isoglutamine

Topics

• Acetylmuramyl-Alanyl-Isoglutamine (administration & dosage, analogs & derivatives, pharmacology)
• Adjuvants, Immunologic (pharmacology)
• Cells, Cultured
• Cytokines (genetics)
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Humans
• Interleukin-1 (genetics)
• Interleukin-6 (genetics)
• Interleukin-8 (genetics)
• Liposomes
• Monocytes (drug effects, metabolism)
• Phosphatidylethanolamines (administration & dosage, pharmacology)
• RNA, Messenger (analysis)
• Transcription, Genetic (drug effects)
• Tumor Necrosis Factor-alpha (genetics)
• Up-Regulation