Immunostimulatory effects of 1-O-acylated derivatives of N-acetyl-muramyl-L-alanyl-D-
isoglutamine (MDP) methyl
ester, with or without the 6-O-phosphoryl group, on augmentation of
IgG antibody response against
influenza hemagglutinin (HA)
vaccine, in vivo macrophage activation and enhancement of non-specific host resistance against
Pseudomonas aeruginosa infection were investigated. The activities were tested intraperitoneally (i.p.) in mice administered test samples solubilized or suspended in saline. The introduction of longer chain acyl groups into MDP methyl
esters significantly induced enhancement of the
IgG antibody response. Among them, the adjuvant activity of 1-O-linked 2-tetradecylhexadecanoyl
(B30)-MDP methyl
ester was comparable to that of 6-O-B30-MDP used as a positive control. Phosphorylation at the C6 position of the acylated MDP analogs did not induce a significant increment in the activity. With respect to phagocytic, cellular
acid phosphatase and cytostasis-inducing activities, i.p. administration of acylated MDP analogs caused significant increment and activation of peritoneal macrophages. The cytostasis-inducing activity of 1-O-octadecanoyl- or 1-O-B30-MDP methyl
ester with or without a phosphoryl group was more intensive than that of 6-O-B30-MDP. Acylated MDP analogs enhanced non-specific resistance against P. aeruginosa
infection when the analogs were administered i.p. on the day before the
infection. The enhancement was closely related to the accumulation of polymorphonuclear cells in the peritoneal cavity. The manifestation of these immunostimulatory activities by 1-O-acylated MDP analogs depended closely on the increasing
carbon chain length of
fatty acid substituents when administered in aqueous form.