Effects of nontoxic lipid A and endotoxin on resistance of mice to Toxoplasma gondii.

Mice were administered nontoxic monophosphoryl lipid A (MPL) or refined standard bacterial endotoxin (RSE) prior to, simultaneously with, or after infection with Toxoplasma gondii. MPL and RSE given before or with the toxoplasma infection induced significant resistance. Administration of toxic RSE, but not nontoxic MPL, after the establishment of toxoplasma infection significantly shortened the survival time of mice.

Glycolipid induced proliferation of lipopolysaccharide hyporesponsive C3H/HeJ splenocytes.

Although the C3H/HeJ mouse is hyporesponsive to lipopolysaccharides (LPS), certain forms of the lipid A fraction have been shown to stimulate cells from this mouse strain. To determine the role of the oligosaccharide chain length on the lipid A-induced proliferation of C3H/HeJ splenocytes, a panel of glycolipids from R-chemotypes (Re, Rc, and Rd) and a nontoxic monophosphoryl lipid A (MPL) were tested. The MPL cells isolated from the MPL of Salmonella minnesota, Salmonella typhimurium, and the Reglycolipids isolated from Escherichia coli were found to be effective at stimulating the LPS-hyporesponsive spleen cells.

Characterization of a nontoxic monophosphoryl lipid A.

Gram-negative bacterial endotoxins constitute some of the strongest immunologic adjuvants known. Precluding their use as adjuvants in humans has been the exquisite toxicity of these compounds in extraordinarily small amounts. With the acquisition of precise knowledge of the structure of the active moiety, detoxifying procedures have been developed.

The adjuvant properties of a nontoxic monophosphoryl lipid A in hyporesponsive and aging mice.

The immunomodulatory action of a nontoxic monophosphoryl lipid A (MPL) and a toxic diphosphoryl lipid A (DPL) fraction derived from endotoxins of the heptoseless mutants of bacteria were studied. Both derivatives retained the ability characteristic of lipopolysaccharides, i.e.

Enhancement of chemiluminescence and phagocytic activities by nontoxic and toxic forms of lipid A.

The effect on the respiratory burst of murine splenic cells after in vitro exposure to nontoxic monophosphoryl lipid A (MPL), toxic diphosphoryl lipid A (DPL), and refined standard endotoxin (RSE) was studied by luminol-dependent, zymosan-stimulated chemiluminescence (CL). CL was stimulated only to a minimum degree by 0.1 micrograms of MPL, DPL, or RSE, but this was clearly increased when 10-fold higher doses were used.