Deficiency of inflammasome components NLRP3, ASC or Caspase-1, or lack of IL-1 signaling prevented alcohol-induced liver inflammation suggesting that IL-1 determines see more the onset of inflammation in AH. Next we evaluated whether IL-1 also drives the persistence of liver inflammation in AH. We observed that liver

inflammation and increased IL-1 were sustained for at least three days after cessation of alcohol, followed by delayed apoptosis of inflammatory cells in the liver and limited degree of hepatocyte regeneration. We discovered that inhibition of IL-1 signaling using a single dose of IL-1Ra at cessation of alcohol increased apoptosis of liver immune cells, facilitated regeneration of hepatocytes, and resulted in increased rate of recovery from liver injury in AH. These findings were consistent with in vitro studies showing that IL-1 administration Wee1 inhibitor promotes cytotoxicity of primary hepatocytes while it provides pro-survival benefit for BM-derived immune cells Conclusions: Our novel findings demonstrate that IL-1 drives sustained liver inflammation

and impaired hepatocyte regeneration even after cessation of ethanol exposure in AH. Therapeutic inhibition of IL-1 improves hepatocyte survival and promotes death of activated harmful immune cells in a preclin-ical model of AH. Disclosures: Gyongyi Szabo – Consulting: Idenix; Grant/Research Support: BMS, GSK, Cona-tus, Idera, Johnson&Johnson, Novartis, Ocera, Roche, Shering – Plough, Wyeth, Integrated 4��8C Therapeutics, Idera The following people have nothing to disclose: Jan Petrasek, Arvin Irache-ta-Vellve, Shashi Bala, Timea Csak, Karen Kodys, Evelyn A. Kurt-Jones Background: Epidemiological studies revealed that nearly 80% of heavy drinkers with alcoholic liver disease (ALD) also smoke tobacco. This finding suggests that tobacco and possibly its toxins have cofactor roles in ALD pathogenesis. Our research focused on the potential role of NNK as a mediator

of hepa-tocellular injury in ALD because previous efforts showed that other nitrosamines can cause hepatic steatosis or steatohep-atitis with insulin resistance, inflammation, oxidative and ER stress, and lipotoxicity. Moreover, toxic lipids, particularly ceramides, can promote the same effects. Due to the inability to detect significant molecular profiles by routine histological studies, we explored the potential use of matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry as a diagnostic aid for characterizing the nature and possibly etiology of steatohepatitis. Hypothesis: IMS can be used to generate biochemical signatures of steatohepatitis caused by different agents.