IMMUNOBIOLOGICAL ACTIVITIES OF CHEMICALLY-DEFINED LIPID-A FROM LIPOPOLYSACCHARIDES OF PORPHYROMONAS-GINGIVALIS

Immunobiological activities of chemically defined lipid A from lipopolysaccharides (LPS) of Porphyromonas gingivalis strain 381, which possesses beta-(1-->6)-linked glucosamine disaccharide l-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 Escherichia coli-type lipid A (compound 506) and Salmonella-type lipid A (compound 516). P. gingivalis 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-gamma as compared with compounds 506 and 516 in the culture supernatants of human peripheral blood monocytes or mononuclear cells. However, the P. gingivalis preparations showed low activity in inducing the production of IL-1 beta and tumour necrosis factor-alpha. Clear antagonistic effects of P. gingivalis lipid A and its LPS against IL-1 beta production induced by E. coli LPS or compound 506 were seen. Furthermore, P. gingivalis 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 P. gingivalis 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.