Immunopharmacological activities of the nontoxic monophosphoryl lipid A of Porphyromonas gingivalis.

The low endotoxic lipid A derived from Porphyromonas gingivalis 381, 1-phospho beta(1-6)-linked glucosamine disaccharide with 3-hydroxy-15-methylhexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2- and 2'-positions, respectively, induced mitogenic responses in LPS low responder C3H/HeJ as well as LPS responder C3H/HeN mouse splenocytes. The mitogenic activities of P. gingivalis lipid A in splenocytes of LPS responder mice were comparable to that of the synthetic Escherichia coli-type lipid A (compound 506). The addition of polymyxin B resulted in the inhibition of mitogenic activity. P. gingivalis lipid A also stimulated strongly nonspecific host resistance against Pseudomonas aeruginosa infection in BALB/c mice, and specific immune response in guinea pigs against infection with P. gingivalis. Furthermore, P. gingivalis lipid A demonstrated antitumour activity against MH134 hepatoma in C3H/HeN mice. These life-preserving with tumour regression properties were comparable to those of monophosphoryl lipid A derived from Salmonella minnesota Re 595. Thus, P. gingivalis lipid A appears to have beneficial properties as an immunopharmacological agent.