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.