Stimulation of non-specific resistance to infection by muroctasin.
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)
Otani
T
T
Research Institute, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Une
T
T
Osada
Y
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D007113:Immunity, Innate / Q000187:drug effects*; D007239:Infections / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide