Immunobiological activities of chemically defined lipid A from lipopolysaccharides (LPS) of strain 381, which possesses β-(1·6)-linked glucosamine disaccharide 1-monophosphate, with 3-hydroxy-15-methylhexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2- and 2′ -positions, respectively, were compared with those of synthetic -type lipid A (compound 506) and A (compound 516). lipid A and its LPS induced stronger or comparable production of the cytokines interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, granulocyte-macrophage colony-stimulating factor and interferon-γ as compared with compounds 506 and 516 in the culture supernatants of human peripheral blood monocytes or mononuclear cells. However, the preparations showed low activity in inducing the production of IL-1β and tumour necrosis factor-α. Clear antagonistic effects of lipid A and its LPS against IL-1β production induced by LPS or compound 506 were seen. Furthermore, lipid A and its LPS had marked immunopharmacological activities, i.e. antitumour, natural killer cell and antiviral activities. Its monophosphorylation pattern and the presence and position of fatty acids possessing acyl chains of considerable length are unique to lipid A, differing from enterobacterial lipid As. Its good balance between agonistic and antagonistic effects, making it a possible candidate for use as an immunomodulatory drug, may be attributable to these unique features.


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