romurtide and Infections

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Bacterial Infections; Cytokines; Drug Synergism; Hematopoiesis; Humans; Infections; Leukopenia; Mice; Mycoses; Neoplasms; Virus Diseases

It is well recognized that immunoadjuvants mainly play two roles; non-specific stimulation of host resistance against infections and cancer, and the potentiation of vaccine immunogenicity. This article reviews the recent results of the development of synthetic immunoadjuvants in our laboratory with special reference to muramyldipeptide (MDP), trehalose dimycolate (TDM), lipid A, chitin and their related compounds. The usefulness of MDP derivative MDP-Lys(L18), which has recently gone on the market as a haematopoietic agent for restoration of leukopenia in cancer patients treated with radiotherapy and chemotherapy, is reviewed. The various approaches to application of synthetic immunoadjuvants to the potentiation of vaccine immunogenicity, including adjuvant formulation, are also discussed.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Amino Acid Sequence; Animals; Chitin; Cord Factors; Drug Carriers; Forecasting; Humans; Immunity, Innate; Infections; Lipid A; Molecular Sequence Data; Vaccines

We have reported that the bacterial cell-wall skeletons, such as mycobacteria, nocardia, corynebacteria, propionibacteria and listeria, had potent adjuvant activity on immune responses. It was reported that N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) was the minimum structural requirement of adjuvant activity of the bacterial cell-wall skeleton and a variety of MDP derivatives and related compounds were synthesized. Among the synthetic MDP derivatives, we have selected MDP-Lys(L18)(romurtide) as the immunostimulant, by using experimental models for non-specific host resistance against Escherichia coli in mice. Romurtide was shown to have host-stimulating activity against bacterial, fungal and viral infections, cytokine producing activity and the capacity to increase the number of leukocytes and platelets in experimental models. It was also shown that the clinical effectiveness of romurtide on the restoration of the number of leukocytes and platelets of cancer patients treated with chemotherapy or radiation therapy. The mechanism of action of romurtide is discussed.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Cytokines; Hematopoiesis; Humans; Infections; Leukopenia; Mice; Neoplasms

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)

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Immunity, Innate; Infections