title: Modulation of tumour necrosis factor production with desmuramyldipeptide analogues.
abstract: Some synthetic analogues of the immuno-modulatory agent muramyl dipeptide (MDP), i.e. phthalimido- (LK-511, LK-413, LK-512, LK-423, LK-508), adamantyl- (LK-415, LK-517), 7-oxoaIkyl-(LK-409) desmuramylpeptides were assessed for the tumour necrosis factor (TNF) inducing activity and the ability to modulate TNF production in in vitro phorbol 12-myristate 13-acetate (PMA) & ionomycin stimulated cultures of human peripheral blood mononuclear cells. A kinetic study over a 40-hour period indicated that desmuramyldipeptides were weak TNF inducers compared to romurtide, PMA & ionomycin or lipopolysaccharide. By contrast, they showed the potential to up- or down-regulate the production of TNF evoked by PMA & ionomycin, which was strongly dependent on the time of the stimulation. After 4h of stimulation, the TNF secretion was augmented by LK-508, LK-409 and LK-511, after 18 h by LK-409 and LK-423, and after 40 h by LK-423, LK-511, LK-415 and LK-512. However, LK-517 and LK-512 inhibited the secretion of TNF after the 18-h period.
authors.affiliation: Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia, Slovenia.
authors.forename: Saša
authors.initials: S
authors.lastname: Simčič
authors.affiliation: Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia, Slovenia.
authors.forename: Branka
authors.initials: B
authors.lastname: Wraber
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia, Slovenia.
authors.forename: Marija
authors.initials: M
authors.lastname: Sollner
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia, Slovenia.
authors.forename: Uroš
authors.initials: U
authors.lastname: Urleb
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia, Slovenia.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
keywords: Key words desmuramyldipeptide; immunomodulation; mononuclear cells; phorbol myristate acetate; tumour necrosis factor