Distinctive immunomodulating properties and interactivity with model membranes and cells of two homologous muramyl dipeptide derivatives differing by their lipophilicity

We have studied and compared the immunomodulating activities of two muramyl dipeptide (MDP) derivatives: beta-heptylglycoside-MDP (C(7)H(15)MDP) and beta-hexadecylglycoside-MDP (C(16)H(33)MDP). The amphiphilic derivative C(7)H(15)MDP has been found to be a more effective stimulator of T lymphocyte proliferation and allospecific cytotoxic T cell generation in a mixed lymphocyte culture, and a more effective activator of interleukin-1 (IL-1) and tumour necrosis factor (TNF) production by murine peritoneal macrophages, in comparison with MDP and C(16)H(33)MDP used in equimolar concentrations. C(7)H(15)MDP also stimulated cytotoxicity of natural killer (NK) cells. On the contrary, its lipophilic homologue C(16)H(33)MDP did not show such activities in vitro except for its influence on IL-1 and TNF production. We have found significant differences in the interaction of these two C-14-labelled MDP derivatives with model membranes and in the uptake of these preparations by erythroleukemia K562 cells. We consider the hydrolipophilic balance of the above preparations to be the main cause of their different interactions with membranes and their uptake by cells and, as a result, their opposite immunomodulating activities in vitro. (C) 1997 International Society for Immunopharmacology.