The profile of the stimulant activity of a
muramyl dipeptide (MDP) analog, N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-
L-lysine (MDP-Lys(L18), muroctasin) on the host resistance to
infection was clarified through the following results. A comparative study of parent MDP and
MDP-Lys(L18) in relation to the protection against
infection with various pathogens revealed the same spectrum of antiinfectious activity, but a different potency: the greater strength of
MDP-Lys(L18) was demonstrated both by the smaller influence of bacterial inoculum size on its activity and by the smaller minimal dosage required for inducing significant activity. The superiority of the oral application of
MDP-Lys(L18) over MDP was also demonstrated. The protective activity of the compound was substantially influenced by the timing of treatment, the greatest activity being achieved by treatment 1 day before
infection. Furthermore, treatment with
MDP-Lys(L18) restored the depressed resistance induced by
cyclophosphamide to systemic
infection with E. coli in mice, and that induced by
cortisone acetate to bacteremic
pneumonia with P. aeruginosa in guinea pigs. The chemotherapeutic efficacy of
antibiotics on E. coli
infection was potentiated by combined use of
MDP-Lys(L18) for normal mice and mice immunosuppressed with
cyclophosphamide. From these findings, enhancement of the host resistance to
infection by
MDP-Lys(L18) may be an important aspect in the future evaluation of
therapy for
infection in immunocompromised patients. Finally, since the compound augmented 1. the function of polymorphonuclear leukocytes, such as chemotaxis, phagocytosis, and
superoxide anion generating capacity.(ABSTRACT TRUNCATED AT 250 WORDS)