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.