Majid Afshar1, Stephanie Richards2, Dean Mann3, Alan Cross4, Gordon B Smith5, Giora Netzer6, Elizabeth Kovacs7, Jeffrey Hasday8. 1. Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, 110 S. Paca Street, Baltimore, MD 21202, USA. Electronic address: Majid.afshar@luhs.org. 2. School of Medicine, University of Maryland, 22 S. Greene Street, Baltimore, MD 21202, USA. 3. Department of Pathology, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21202, USA. 4. Center for Vaccine Development, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21202, USA. 5. Shock Trauma and Anesthesiology Research (STAR) Organized Research Center, University of Maryland, 22 S. Greene Street, Baltimore, MD 21202, USA. 6. Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, 110 S. Paca Street, Baltimore, MD 21202, USA; Department of Epidemiology and Public Health, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21202, USA. 7. Alcohol Research Program, Department of Surgery, Loyola University Chicago, Health Sciences Campus, 2160 S. First Avenue, Maywood, IL 60153, USA. 8. Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, 110 S. Paca Street, Baltimore, MD 21202, USA.
Abstract
BACKGROUND: Blood alcohol is present in a third of trauma patients and has been associated with organ dysfunction. In both human studies and in animal models, it is clear that alcohol intoxication exerts immunomodulatory effects several hours to days after exposure, when blood alcohol is no longer detectable. The early immunomodulatory effects of alcohol while blood alcohol is still elevated are not well understood. METHODS: Human volunteers achieved binge alcohol intoxication after high-dose alcohol consumption. Blood was collected for analysis prior to alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow cytometry was performed on isolated peripheral blood mononuclear cells, and cytokine generation in whole blood was measured by enzyme-linked immunosorbent assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and phytohemagglutinin-M (PHA) stimulation. RESULTS: An early pro-inflammatory state was evident at 20 min when blood alcohol levels were ∼130 mg/dL, which was characterized by an increase in total circulating leukocytes, monocytes, and natural killer cells. During this time, a transient increase in LPS-induced tumor necrosis factor (TNF)-α levels and enhanced LPS sensitivity occurred. At 2 and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced numbers of circulating monocytes and natural killer cells, attenuated LPS-induced interleukin (IL)-1β levels, and a trend toward increased interleukin (IL)-10 levels. CONCLUSIONS: A single episode of binge alcohol intoxication exerted effects on the immune system that caused an early and transient pro-inflammatory state followed by an anti-inflammatory state.
BACKGROUND: Blood alcohol is present in a third of traumapatients and has been associated with organ dysfunction. In both human studies and in animal models, it is clear that alcohol intoxication exerts immunomodulatory effects several hours to days after exposure, when blood alcohol is no longer detectable. The early immunomodulatory effects of alcohol while blood alcohol is still elevated are not well understood. METHODS:Human volunteers achieved binge alcohol intoxication after high-dose alcohol consumption. Blood was collected for analysis prior to alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow cytometry was performed on isolated peripheral blood mononuclear cells, and cytokine generation in whole blood was measured by enzyme-linked immunosorbent assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and phytohemagglutinin-M (PHA) stimulation. RESULTS: An early pro-inflammatory state was evident at 20 min when blood alcohol levels were ∼130 mg/dL, which was characterized by an increase in total circulating leukocytes, monocytes, and natural killer cells. During this time, a transient increase in LPS-induced tumor necrosis factor (TNF)-α levels and enhanced LPS sensitivity occurred. At 2 and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced numbers of circulating monocytes and natural killer cells, attenuated LPS-induced interleukin (IL)-1β levels, and a trend toward increased interleukin (IL)-10 levels. CONCLUSIONS: A single episode of binge alcohol intoxication exerted effects on the immune system that caused an early and transient pro-inflammatory state followed by an anti-inflammatory state.
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