The following people have nothing to disclose: Claire Meyer, Sandeep K. Trip-athy Background. It is well known that liver and lung

injury can occur simultaneously during severe inflammation (e.g. multiple organ failure). However, whether these are parallel or interdependent (i.e. liver:lung axis) mechanisms is unclear. Previous studies have shown that chronic alcohol consumption greatly increases the risk of mortality caused by acute respiratory distress syndrome (ARDS). The potential contribution of subclini-cal liver disease driving this effect of ethanol on the lung has not been determined. Therefore, the purpose of this study was to develop a model of concomitant liver and lung injury in the setting of chronic alcohol exposure, followed by an acute inflammatory stimulus. Methods. Male mice were exposed to ethanol-containing Lieber-DeCarli diet or pair-fed control diet for 6w. At the end of the feeding period, some animals were administered LPS to induce MAPK inhibitor ARDS-like lung damage and sacrificed either 4 or 24 h after LPS exposure. The expression of cytokine mRNA in lung and liver tissue were determined by real-time PCR. Cytokine levels in the BAL and plasma were determined by Luminex assay. Changes in the ECM proteome of the liver and lung were determined by LC-MS. Results. As expected, the combination of EtOH and LPS caused liver injury, as indicated

by significantly increased levels of ALT/AST in the plasma. EtOH preexposure also increased the number and SB203580 mouse size of inflammatory foci in the liver tissue caused by LPS. In the lung, EtOH preexposure

enhanced pulmonary inflammation and alveolar hemorrhage caused by LPS exposure. The combination of EtOH and LPS resulted in a unique pro-inflammatory mRNA expression profile in the two organs. As expected, eth-anol preexposure significantly increased hepatic TNFα mRNA expression and increased TNFα levels in the systemic circulation. In contrast, EtOH preexposure significantly increased pulmonary mRNA expression of the TNFα responsive genes MIP-2 and KC in the lung in the absence of a significant increase in TNFα mRNA or protein in lung tissue or BAL fluid, respectively. Additionally, EtOH exposure caused dynamic, transitional changes in the expression of ECM components (e.g. fibrin and fibronectin) in both the liver 上海皓元医药股份有限公司 and lung. Conclusions. EtOH pre-exposure enhanced both liver and lung injury caused by LPS. Enhanced organ injury corresponded with unique changes in the expression of pro-inflammatory cytokines in the liver (i.e. TNFα) and the lung (i.e. MIP-2, KC). EtOH preexposure also contributed to transitional changes in the ECM profile and increased expression of extracellular matrices which may play direct role in enhanced inflammation and injury in the two organs. Jesse Roman – Advisory Committees or Review Panels: Cellgene; Grant/Research Support: Actelion, Intermune, Novartis The following people have nothing to disclose: Veronica L.