cord-factors and squalane

Trehalose dimycolate extracted from mycobacteria is a potent immunomodulator. Incorporation of trehalose dimycolate in a squalane-in-water emulsion leads predominantly to the formation of vesicular structures, which are observable by electron microscopy. The interaction between vesicles of trehalose dimycolate and the immunocompetent cells results in an enhancement of the host defence mechanisms and induction of non-specific resistance against viral, parasitic, and bacterial pathogens and certain tumors. A brief review of the pertinent observations is presented.

Topics: Adjuvants, Immunologic; Animals; Chromatography; Cord Factors; Emulsions; Glycolipids; Humans; Squalene

The effect on natural killer (NK) cytotoxicity of splenic cells from BALB/c mice pretreated i.v. with squalane-in-water preparations of muramyl dipeptide (MDP), trehalose dimycolate (TDM), or the combination of MDP-plus-TDM was investigated. MDP or TDM augmented the NK cytotoxicity which peaked 48 h after the pretreatment whereas the combination of MDP and TDM induced an inhibition of the NK activity. Infection with influenza virus, a potent stimulator of NK cells, after the pretreatment with biological response modifiers resulted in a markedly enhanced NK activity on day 2 in MDP and control groups. Mice pretreated with TDM or the combination of MDP and TDM showed only moderate NK activity which peaked on day 3 after influenza infection. The NK activity was susceptible to asialo GM1 and complement treatment. The cytotoxicity of MDP-plus-TDM cells could be significantly enhanced after treatment with anti-macrophage monoclonal antibody and complement. NK activity induced by MDP or TDM was reduced by mixing MDP-plus-TDM cells. Addition of adherent cell-depleted MDP-plus-TDM suspension to MDP or TDM cells had a NK restorative effect. Splenic cells from mice pretreated 2 days earlier with MDP or TDM, but not MDP-plus-TDM, generated enhanced levels of luminol-dependent chemiluminescence.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Cord Factors; Cytotoxicity, Immunologic; Glycolipids; Killer Cells, Natural; Kinetics; Mice; Mice, Inbred BALB C; Spleen; Squalene; Zymosan

The influence of mineral oil, squalane, squalene, or peanut oil on the antitumor activity of emulsified Bacillus Calmette-Guérin cell walls or emulsified trehalose-6,6'-dimycolate was studied in mice, each with an established transplant of a syngeneic fibrosarcoma. Each animal received an intratumoral injection of Bacillus Calmette-Guérin cell walls (0.6 mg/mouse) or trehalose-6,6'-dimycolate (0.1 mg/mouse) emulsified in 1 to 10% oil. Emulsions of squalene or squalane but not peanut oil were effective substitutes for mineral oil as carriers of Bacillus Calmette-Guérin cell walls in the treatment of the tumor. Trehalose-6,6'-dimycolate was therapeutically active when it was incorporated in any of these four oils. The number of animals in which tumor regressed completely depended on the concentration of oil in the emulsion.

Topics: Animals; Arachis; BCG Vaccine; Cell Wall; Cord Factors; Glycolipids; Male; Mice; Mineral Oil; Oils; Remission, Spontaneous; Sarcoma, Experimental; Squalene