Transfection of NF-kB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy

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Background: Macrophages play an important role in the initiation of the hypercytokinemia that is involved in the development of liver failure after excessive hepatectomy. This study was aimed at evaluating whether the selective suppression of NF-kB in macrophages by decoy oligodeoxynucleotides (ODN) could prevent liver failure after excessive hepatectomy. Materials and Methods: Ninety-percent hepatectomy was performed in 8-week-old mice. NF-KB/decoy/ODN was transfected into the liver by the HVJ-liposome method. The survival rate, serum levels of IL-18, IL-6 and TNF-a, and the histological findings in the remnant liver were compared between the 90%-hepatectomized mice transfected with the decoy ODN (decoy group) and the 90%-hepatectomized mice injected with saline (control group) . Result: The control group mice died within 48 hours of the operation, while the survival rate in the decoy group at 48 hours after the operation was 35%, and at 2 weeks, 15%. The serum levels of all cytokines were significantly lower in the decoy group than in the control group. The number of TUNEL-positive cells in the remnant liver was smaller in the decoy group. Conclusion: Transfection of NF-kB/decoy/ODN reduces fatal liver failure in mice after excessive hepatectomy by suppressing hypercytokinemia, but offers only a low rate of survival.(199 words)