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The direct action of ethanol on reactive oxygen intermediates (ROI) production has been clearly implicated in ethanol toxicity; however, several studies have demonstrated a role for acetaldehyde in the oxidative damage. All tissues in the body are affected by exposure to ethanol, and variations in the toxic effects may be a reflection of the ROI/reactive nitrogen intermediates generating mechanisms available in that tissue as well as the level of antioxidant protection. Diminished energy production and the formation of free radicals following hypoxia are believed to underlie cellular damage and the ensuing teratogenic effects. The effect is varied, however, and depends on the duration of exposure, the concentration of alcohol, and the type of agent used to induce ROI production. Although alcohol-induced oxidant stress and the consequent tissue injury have been described, little is known about the mechanisms by which ethanol induces tissue damage.

This article summarizes content proceedings of a satellite meeting held at the 2004 Research Society on Alcoholism Annual Scientific Meeting in Vancouver, Canada. The aim of the satellite conference was to facilitate the interaction of scientists investigating the mechanisms of alcohol-mediated organ or tissue damage, and enable the discussion and sharing of new ideas and concepts that may be common in each of the organs or tissues affected by chronic ethanol consumption. The original planned program on immunity was expanded to incorporate a session on a closely related topic "Alcohol and Mitochondrial Metabolism: At the Crossroads of Life and Death" organized by Dr. Jan Hoek and Dr. Sam Zakhari. The conference was arranged into four sessions: 1) Alcohol, Cellular and Organ Damage 2) Toll-like receptors and Organ Damage 3) Alcohol and Mitochondrial Metabolism: At the Crossroads of Life and Death and 4) Hepatitis virus and alcohol interactions in Immunity and Liver Disease. The keynote address was given by Dr. Bruce Beutler from the Scripps Institute on "TLRs in Inflammation and Immunity."The Combined Basic Research Satellite Symposium entitled, "Mechanisms of Alcohol-Mediated Organ and Tissue Damage: Inflammation and Immunity and Alcohol and Mitochondrial Metabolism: At the Crossroads of Life and Death" was convened at the 2004 Research Society on Alcoholism meeting in Vancouver, BC. Session One featured five speakers who discussed various aspects of the role of the immune system in initiating or exacerbating cellular and organ damage following alcohol consumption. The presentations were (1) Innate Immune responses of Alcohol-exposed mice and macrophage-like cells following infections with Listeria monocytogenes by Robert T. Cook 2) Alcohol, cytokines and host defense by Kyle Happel 3) Decreased antigen presentation and anergy induced by alcohol in myeloid dendritic cells by Pranoti Mandrekar 4) Transcriptional regulation of TNF-alpha in human monocytes by chronic ethanol: role of the cellular redox state by Jay Kolls 5) Estrogen and gender differences in inflammatory responses after alcohol and burn injury by Elizabeth Kovacs. This session highlighted the growing information on the role of pattern recognition molecules in alcohol-mediated tissue damage or dysfunction. The new techniques and ideas presented will be helpful in future studies in this area of research, and should result in some exciting avenues of study.

This article summarizes the proceedings of a symposium held at the 2002 Research Society on Alcoholism Meeting in San Francisco, California. The aim of this symposium was to review research on the effects of ethanol on neural stems cells and neurogenesis. Ethanol is known to alter neurogenesis during development; however, recent studies indicate that the brain forms new neurons from stem cells throughout life. Furthermore, stem cells can be transplanted into the brain, creating exciting new possibilities to study brain function. The symposium covered these research areas. Dr. Michael W. Miller reviewed knowledge on the effects of ethanol on stem cell proliferation and differentiation during development. Dr. Wu Ma described studies in culture indicating that (1) neural stem cells express functional muscarinic acetylcholine receptors (mAchR), (2) mAchR-mediated proliferation involves Ca signaling and mitogen-activated protein kinase phosphorylation, and (3) phosphoinositol-3 kinase is a downstream effector for mAchR-mediated cell proliferation via activation of Akt. Drs. Kim Nixon and Fulton T. Crews followed with in vivo studies on ethanol's effects on adult neural stem cell proliferation and differentiation. Dr. W. Michael Zawada described studies directed at dopamine neuron cell transplants into mammalian central nervous system. These studies clearly establish that ethanol has significant effects on stem cells.

Moderate alcohol consumption (1-2 drinks a day) can be beneficial in reducing the risk of coronary artery disease. This article focuses on cellular and molecular mechanisms underlying the beneficial effect of moderate drinking, including increased plasma high-density lipoprotein levels, changes in cellular signaling, reduction in platelet function, stimulation of fibrinolysis, and reduction in ischemia-reperfusion injury. While moderate drinking may be protective against coronary artery disease for some individuals, populations such as pregnant women and individuals who are about to operate motor vehicles or heavy machinery should not drink alcoholic beverages. People with family histories of alcoholism should exercise extreme caution in their decision to drink.

Pancreatitis occurs when digestive enzymes are activated in the pancreas. Severe pancreatitis has a 10-30% mortality rate. No specific treatments for pancreatitis exist now. Here, we discovered that interleukin-22 (IL-22) may have therapeutic potential in treating acute and chronic pancreatitis. Wild-type and IL-22 knockout mice were equally susceptible to cerulein-induced acute and chronic pancreatitis, whereas liver-specific IL-22 transgenic mice were completely resistant to cerulein-induced elevation of serum digestive enzymes, pancreatic necrosis and apoptosis, and inflammatory cell infiltration. Treatment of wild-type mice with recombinant IL-22 or adenovirus IL-22 markedly attenuated the severity of cerulein-induced acute and chronic pancreatitis. Mechanistically, we show that the protective effect of IL-22 on pancreatitis was mediated via the induction of Bcl-2 and Bcl-X(L), which bind to Beclin-1 and subsequently inhibit autophagosome formation to ameliorate pancreatitis. In conclusion, IL-22 ameliorates cerulein-induced pancreatitis by inhibiting the autophagic pathway. IL-22 could be a promising therapeutic drug to treat pancreatitis.

Hepatitis C viral infection (HCV) results in liver damage leading to inflammation and fibrosis of the liver and increasing rates of hepatic decompensation and hepatocellular carcinoma (HCC). However, the host's immune response and viral determinants of liver disease progression are poorly understood. This review will address the determinants of liver injury in chronic HCV infection and the risk factors leading to rapid disease progression. We aim to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. We will accomplish this task by discussion of three topics: (1) the role of cytokines in the adaptive immune response against the HCV infection; (2) the progression of fibrosis; and (3) the risk factors of co-morbidity with alcohol and human immunodeficiency virus (HIV) in HCV-infected individuals. Despite recent improvements in treating HCV infection using pegylated interferon alpha (PEGIFN-alpha) and ribavirin, about half of individuals infected with some genotypes, for example genotypes 1 and 4, will not respond to treatment or cannot be treated because of contraindications. This review will also aim to describe the importance of IFN-alpha-based therapies in HCV infection, ways of monitoring them, and associated complications.

Pancreatitis occurs when digestive enzymes are activated in the pancreas. Severe pancreatitis has a 10-30% mortality rate. No specific treatments for pancreatitis exist now. Here, we discovered that interleukin-22 (IL-22) may have therapeutic potential in treating acute and chronic pancreatitis. Wild-type and IL-22 knockout mice were equally susceptible to ceru-lein-induced acute and chronic pancreatitis, whereas liver-specific IL-22 transgenic mice were completely resistant to cerulein-induced elevation of serum digestive enzymes, pancreatic necrosis and apoptosis, and inflammatory cell infiltration. Treatment of wild-type mice with recombinant IL-22 or adenovirus IL-22 markedly attenuated the severity of cerulein-induced acute and chronic pancreatitis. Mechanistically, we show that the protective effect of IL-22 on pancreatitis was mediated via the induction of Bcl-2 and Bcl-XL, which bind to Beclin-1 and subsequently inhibit autophagosome formation to ameliorate pancreatitis. In conclusion, IL-22 ameliorates cerulein-induced pancreatitis by inhibiting the autophagic pathway. IL-22 could be a promising therapeutic drug to treat pancreatitis.