Endotoxin syndrome is a systemic inflammatory response mediated by inflammatory cytokines. Nuclear factor B (NF-B) is the dominant regulator of the production of these cytokines by inflammatory cells. The aim of this study was to assess the efficacy of in vivo transfer of synthetic double-stranded oligodeoxynucleotides (ODN) with high affinity against NF-B (NF-B/decoy/ODN) as a therapeutic strategy for treating endotoxin-induced fatal liver injury. Liver injury was induced by administration of lipopolysaccharide (LPS) to Propionibacterium acnes-primed BALB/C mice. NF-B/decoy/ODN was transferred into the portal vein using a fusigenic liposome with hemagglutinating virus of Japan. NF-B/decoy/ODN was preferentially transferred to Kupffer cells, and activation of NF-B after the LPS challenge was suppressed, leading to decreased inflammatory cytokine production. As a result, the massive necrosis and hepatocyte apoptosis observed in the control mice was dramatically attenuated and the survival rate improved. In conclusion, NF-B/decoy/ ODN transfer in vivo effectively suppressed endotoxin-induced fatal liver injury in mice. (HEPATOLOGY 2003;38:335-344.)

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