AIM:To investigate urotensin-Ⅱ(UⅡ) and its effects on tumor necrosis factor(TNF)-α and interleukin(IL)-1β in early acute liver failure(ALF).METHODS:We investigated the time-dependent alteration in UⅡ levels and its effects on TNF-αand IL-1β in liver and blood in the early stage of lipopolysaccharide/D-galactosamine-induced ALF.RESULTS:After lipopolysaccharide/D-galactosamine challenge,UⅡ rose very rapidly and reached a maximal level 0.5 h,and the level remained significantly elevated after 2 h(P < 0.05).Six hours after challenge,UⅡ began to degrade,but remained higher than at 0 h(P < 0.05).Pretreatment with urantide,an inhibitor of the UⅡ receptor,suppressed the degree of UⅡ increase in liver and blood at 6 h after challenge(P < 0.05 vs paired controls).In addition,liver and blood TNF-α increased from 1 to 6 h,and reached a peak at 1 and 2 h,respectively; however,IL-1β did not rise until 6 h after challenge.Urantide pretreatment inhibited the degree of TNF-α and IL-1β increase following downregulation of UⅡ post-challenge(all P < 0.05).CONCLUSION:UⅡ plays a role in the pathogenesis and priming of ALF by triggering an inflammatory cascade and driving the early release of cytokines in mice. AIM: To investigate urotensin-Ⅱ (UⅡ) and its effects on tumor necrosis factor (TNF) -α and interleukin (IL) -1β in early acute liver failure (ALF). METHODS: We investigated the time-dependent alteration in UⅡ levels and its effects on TNF-αand IL-1β in liver and blood in the early stage of lipopolysaccharide / D-galactosamine-induced ALF.RESULTS: After lipopolysaccharide / D-galactosamine challenge, UII rose very rapidly and reached a maximal level 0.5 h, and the level remained significantly elevated after 2 h (P <0.05). Six hours after challenge, UII started to degrade, but remained higher than at 0 h (P <0.05). Pretreatment with urantide, an inhibitor of the UII receptor, suppressed the degree of UII increase in liver and blood at 6 h after challenge (P <0.05 vs. paired controls) .In addition, liver and blood TNF-α increased from 1 to 6 h, and reached a peak at 1 and 2 h, respectively ; however, IL-1β did not rise until 6 h after challenge. Urantide pretreatment inhibited the degree of TNF-α and IL -1β increase following downregulation of UII post-challenge (all P <0.05) .CONCLUSION: UII plays a role in the pathogenesis and priming of ALF by triggering an inflammatory cascade and driving the early release of cytokines in mice.