Published online Mar 21, 2015. doi: 10.3748/wjg.v21.i11.3239
Peer-review started: July 8, 2014
First decision: September 15, 2014
Revised: October 23, 2014
Accepted: December 16, 2014
Article in press: December 16, 2014
Published online: March 21, 2015
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-α and 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.
Core tip: In this study, we found that urotensin-II (UII) increased before tumor necrosis factor (TNF)-α and interleukin (IL)-1β following lipopolysaccharide/D-galactosamine challenge. Furthermore, pretreatment with urantide, an inhibitor of the UII receptor, blocked TNF-α and IL-1β increases following downregulation of UII in liver and blood at different time points after challenge. Therefore, UII may play a pivotal role in the pathogenesis and priming of acute liver failure by triggering the inflammatory cascade, and initiating and driving the early release of TNF-α and IL-1β in lipopolysaccharide/D-galactosamine-challenged mice.