Adjuvant activities of synthetic lipid A subunit analogues and its conjugates with muramyl dipeptide derivatives.
We investigated the effects of the active principle of lipopolysaccharide (LPS), synthetic lipid A (compound 506), and of its related compounds GLA-60, -59 and -27, on murine macrophage activation and cytokine induction. GLA-60, which is devoid of endotoxic activity, showed interleukin-1 (IL-1)-inducing activity and activation of murine macrophages comparable to those of LPS or compound 506. The biological activities of six conjugates of GLA-60 with MDP derivatives GMD-323 to -328 were investigated in this study. All the GMD compounds except GMD-323 showed potent inducing activities for IL-1 and tumoricidal macrophages, especially GMD-324 and -326, which exhibited much higher activity than GLA-60. However, TNF- and CSF-inducing activities of these conjugates were lower than those of GLA-60. IL-1-inducing activity of the mixture of MDP derivative (GMD-267) and GLA-60 was higher than that of the conjugates (GMD-324) or that of GLA-60 and GMD-267 alone.
Maeda
H
H
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Saiki
I
I
Ishida
H
H
Kiso
M
M
Hasegawa
A
A
Azuma
I
I
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004926:Escherichia coli; D007375:Interleukin-1 / Q000096:biosynthesis; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C056260:GLA 60; D000119:Acetylmuramyl-Alanyl-Isoglutamine