A comparison of the immunomodulating properties of two forms of monophosphoryl lipid A analogues.
This investigation compared the immunomodulating activities of two forms monophosphoryl lipid A, which are analogues of bacterial lipopolysaccharides with little or no toxicity. Tested were a synthetic compound designated 504 and a purified compound, isolated from bacterial cell walls designated MPL. Both of these clinical adjuvant candidates were effective in mice in exerting strong immunomodulating activity in the following areas: (a) enhancing antibody production in young and aging mice; (b) suppressing antibody formation under different experimental conditions; (c) activating macrophages to secrete interleukin 1, hydrogen peroxide, and superoxide anion; and (d) stimulating proliferation of spleen cells from C3H/HeN mice. Both exhibited considerably reduced toxicity in LD50 assays when compared to native lipopolysaccharides (LPS). The LD50 for MPL was 225 times and that of compound 504, 40 times that of native LPS in the exquisitely sensitive, galactosamine-loaded C57BL/6 murine strain.
Johnson
A G
AG
Department of Medical Microbiology/Immunology, University of Minnesota, Duluth 55812.
Tomai
M A
MA
Chen
Y F
YF
Odean
M
M
D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000375:Aging / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008050:Lipid A / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000276:Adjuvants, Immunologic; D008050:Lipid A; C048436:monophosphoryl lipid A