romurtide and Hepatitis-B

N(2)-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N(6)-trans-(m-nitrocinnamoyl)-L-lysine (muramyl dipeptide C, or MDP-C) has been synthesized as a novel, nonspecific immunomodulator. The present study shows that MDP-C induces strong cytolytic activity by macrophages on P388 leukemia cells and cytotoxic activity by cytotoxic T lymphocytes (CTLs) on P815 mastocytoma cells. Our results also indicate that MDP-C is an effective stimulator for production of interleukin-2 and interleukin-12 by murine bone marrow derived dendritic cells (BMDCs) and production of interferon-gamma by CTLs. Additionally, MDP-C increases the expression levels of several surface molecules, including CD11c, MHC class I, and intercellular adhesion molecule-1 in BMDCs. Moreover, MDP-C remarkably enhances the immune system's responsiveness to hepatitis B surface antigen (HBsAg) in hepatitis B virus transgenic mice for both antibody production and specific HBsAg T-cell responses ex vivo. Our results indicate that MDP-C is an apyrogenic, nonallergenic, and low-toxicity immunostimulator with great potential for diagnostic, immunotherapeutic, and prophylactic applications in diseases such as hepatitis B and cancers.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Antibody Formation; Bone Marrow Cells; CD11c Antigen; Cell Line, Tumor; Cytotoxicity, Immunologic; Dendritic Cells; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Histocompatibility Antigens Class I; In Vitro Techniques; Intercellular Adhesion Molecule-1; Interleukin-12; Interleukin-2; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Rabbits; Rats; Rats, Wistar; T-Lymphocytes, Cytotoxic; Toxicity Tests, Acute