TNF-alpha production-enhancing activity of 2-(1-adamantylamino)-6-methylpyridine (AdAMP) in cultures of human normal and neoplastic cells.
The purpose of this study was to determine the TNF-alpha-stimulatory effect of a novel immunomodulator 2-(1-adamantylamino)-6-methylpyridine (AdAMP) on normal and neoplastic human cells. In a panel of several human ovarian cancer cell lines, almost half of them spontaneously secreted significant amounts of TNF-alpha. When incubated with AdAMP, a 3-fold enhancement of TNF-alpha production by cells was observed. Furthermore, the phorbol myristic acetate ester (PMA)-induced release of TNF-alpha in cultures of U937 cells was increased in the presence of AdAMP. Primary monocytes isolated from peripheral blood did not respond to AdAMP. Although cytokine release was not triggered in human peripheral blood monocytes, AdAMP co-stimulated these cells to produce TNF-alpha and IL-8 during incubation with lipopolysaccharide (LPS). No effect of AdAMP was found on IL-1beta and IL-6 production by monocytes. In cultures of peripheral blood T lymphocytes, AdAMP significantly decreased the adhesion of these cells to matrix proteins in an in vitro assay. The results suggest that AdAMP, as a stimulator of cytokine secretion, may have potential application in tumor therapy.
Hareng
Lars
L
Biochemical Pharmacology, University of Konstanz, Germany.
Lasek
Witold
W
Switaj
Tomasz
T
Sienko
Jacek
J
Jakubowska
Anna B
AB
Nowaczyk
Maria
M
Kasprzycka
Monika
M
Kazimierczuk
Zygmunt
Z
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
C466498:2-(1-adamantylamino)-6-methylpyridine; D000631:Aminopyridines; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000218:Adamantane