Lauren G Poole1, Juliane I Beier2, Edilson Torres-Gonzales3, Connie F Schlueter4, Shanice V Hudson1, Amanda Artis5, Nikole L Warner6, Calvin T Nguyen-Ho1, Christine E Dolin1, Jeffrey D Ritzenthaler3, Gary W Hoyle4, Jesse Roman7, Gavin E Arteel8. 1. Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States. 2. Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States; University of Louisville Hepatobiology and Toxicology Program, Louisville, KY, 40292, United States. 3. Department of Medicine, Division of Pulmonary, Critical Care and Sleep Disorders Medicine, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States. 4. Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States. 5. Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, 10065, United States. 6. Department of Microbiology and Immunology, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States. 7. Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States; Department of Medicine, Division of Pulmonary, Critical Care and Sleep Disorders Medicine, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States; University of Louisville Alcohol Research Center, Louisville, KY, 40292, United States. 8. Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY, 40292, United States; University of Louisville Alcohol Research Center, Louisville, KY, 40292, United States. Electronic address: gearteel@pitt.edu.
Abstract
INTRODUCTION: Alcohol use disorders are major risk factors for the development of and susceptibility to acute respiratory distress syndrome. Although these risks of alcohol consumption on the lung are well described, mechanisms by which alcohol abuse promotes acute lung injury are poorly understood. These gaps in our understanding are due, at least in part, to limitations of animal models to recapitulate human alcohol consumption. Recently, a new model of chronic plus binge alcohol exposure was developed that is hypothesized to better model drinking patterns of individuals with alcohol use disorders. Specifically, this paradigm models chronic consumption coupled with periodic bouts of heavy drinking. The impacts of this alcohol-exposure regimen on the lung are uncharacterized. Therefore, the goal of this study was to examine lung injury and inflammation in a well-characterized experimental model of chronic + binge alcohol exposure. METHODS: 10-week-old male C57Bl6/J mice were administered ethanol-containing (or isocaloric control) liquid diet for 10 days, followed by a single ethanol gavage (5 g/kg). Lung inflammation and pulmonary function were assessed. RESULTS: Ten days of ethanol-containing liquid diet alone (chronic) did not detectably affect any variables measured. However, ethanol diet plus gavage (chronic + binge) caused neutrophils to accumulate in the lung tissue and in the bronchoalveolar lavage fluid 24 h post-binge. This inflammatory cell recruitment was associated with airway hyper-responsiveness to inhaled methacholine, as indicated by elevated resistance, Newtonian resistance, and respiratory resistance. CONCLUSIONS: Taken together, the novel findings reveal that ethanol alone, absent of any secondary inflammatory insult, is sufficient to produce inflammation in the lung. Although these changes were relatively mild, they were associated with functional changes in the central airways. This animal model may be useful in the future for identifying mechanisms by which alcohol abuse sensitizes at-risk individuals to lung injury.
INTRODUCTION:Alcohol use disorders are major risk factors for the development of and susceptibility to acute respiratory distress syndrome. Although these risks of alcohol consumption on the lung are well described, mechanisms by which alcohol abuse promotes acute lung injury are poorly understood. These gaps in our understanding are due, at least in part, to limitations of animal models to recapitulate humanalcohol consumption. Recently, a new model of chronic plus binge alcohol exposure was developed that is hypothesized to better model drinking patterns of individuals with alcohol use disorders. Specifically, this paradigm models chronic consumption coupled with periodic bouts of heavy drinking. The impacts of this alcohol-exposure regimen on the lung are uncharacterized. Therefore, the goal of this study was to examine lung injury and inflammation in a well-characterized experimental model of chronic + binge alcohol exposure. METHODS: 10-week-old male C57Bl6/J mice were administered ethanol-containing (or isocaloric control) liquid diet for 10 days, followed by a single ethanol gavage (5 g/kg). Lung inflammation and pulmonary function were assessed. RESULTS: Ten days of ethanol-containing liquid diet alone (chronic) did not detectably affect any variables measured. However, ethanol diet plus gavage (chronic + binge) caused neutrophils to accumulate in the lung tissue and in the bronchoalveolar lavage fluid 24 h post-binge. This inflammatory cell recruitment was associated with airway hyper-responsiveness to inhaled methacholine, as indicated by elevated resistance, Newtonian resistance, and respiratory resistance. CONCLUSIONS: Taken together, the novel findings reveal that ethanol alone, absent of any secondary inflammatory insult, is sufficient to produce inflammation in the lung. Although these changes were relatively mild, they were associated with functional changes in the central airways. This animal model may be useful in the future for identifying mechanisms by which alcohol abuse sensitizes at-risk individuals to lung injury.
Authors: Samantha M Yeligar; Michael M Chen; Elizabeth J Kovacs; Joseph H Sisson; Ellen L Burnham; Lou Ann S Brown Journal: Alcohol Date: 2016-09-16 Impact factor: 2.405
Authors: Juliane I Beier; James P Luyendyk; Luping Guo; Claudia von Montfort; Donald E Staunton; Gavin E Arteel Journal: Hepatology Date: 2009-05 Impact factor: 17.425
Authors: Lokendra Thakur; Marija Kojicic; Sweta J Thakur; Matthew S Pieper; Rahul Kashyap; Cesar A Trillo-Alvarez; Fernandez Javier; Rodrigo Cartin-Ceba; Ognjen Gajic Journal: Int J Environ Res Public Health Date: 2009-09-10 Impact factor: 3.390