Enhancement by muramyldipeptides of the activities of early-type inducers of interferon.
A synthetic muramyldipeptide (MDP) and two analogues, B30-MDP and MDP-Lys(L18), augmented serum interferon (IFN) production in mice by the inducers lipopolysaccharide (LPS) and polyinosinic acid:polycytidylic acid (poly I:C), and also augmented immune IFN production induced by purified protein derivative (PPD) in mycobacteria-sensitized mice. These compounds were most effective when administered to mice one day before the interferon inducer. By contrast, IFN production in mice by either oral tilorone or virus infection was not enhanced with these compounds. Since LPS and poly I:C are well known as early-type IFN inducers, and tilorone and virus infection are late-type inducers, we presume that MDP and its analogues are able to augment only early-type IFN production. This enhancing effect may be mediated by macrophage activation. In vivo antiviral activity of MDP and its analogues was further tested in mice infected with vaccinia virus (VV) using early-type inducers. When mice previously treated with MDP or its analogues were stimulated for IFN production with a low dose of LPS, protective activity against VV infection was markedly enhanced.
S
S
Ikeda
Y
Y
Matsuda
C
C
Nishimura
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005260:Female; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007372:Interferons / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D013994:Tilorone / Q000276:immunology / Q000494:pharmacology; D014615:Vaccinia / Q000276:immunology / Q000628:therapy
D007369:Interferon Inducers; D008070:Lipopolysaccharides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C044706:B 30-muramyl dipeptide; D007371:Interferon-gamma; D007372:Interferons; D013994:Tilorone; D011070:Poly I-C; C036866:romurtide