title: Alveolar macrophage inflammatory mediator expression is elevated in the setting of alcohol use disorders.
abstract: Alcohol use disorders (AUDs) are associated with increased susceptibility to pulmonary diseases, including bacterial pneumonia and acute respiratory distress syndrome (ARDS). Alveolar macrophages (AMs) play a vital role in the clearance of pathogens and regulation of inflammation, but these functions may be impaired in the setting of alcohol exposure. We examined the effect of AUDs on profiles of cytokines, chemokines, and growth factors in human AMs isolated from bronchoalveolar lavage (BAL) samples from 19 AUD subjects and 20 age-, sex-, and smoking-matched control subjects. By multiplex bead array, the lysates of AMs from subjects with AUDs had significant elevation in the cytokine tumor necrosis factor α (TNF-α), as well as chemokine (C-X-C motif) ligand 8 (CXCL8), CXCL10, and chemokine (C-C motif) ligand 5 (CCL5) (p < 0.05). Additionally, a 1.8-fold increase in IL-1β, 2.0-fold increase in IL-6, 2.3-fold increase in interferon gamma (IFN-γ), 1.4-fold increase in CCL3, and a 2.3-fold increase in CCL4 was observed in the AUD group as compared to the control group. We also observed compensatory increases in the anti-inflammatory cytokine IL-1RA (p < 0.05). AUD subjects had 5-fold higher levels of CXCL11 mRNA expression (p < 0.05) and a 2.4-fold increase in IL-6 mRNA expression by RT-PCR as well. In these investigations, alcohol use disorders were associated with functional changes in human AMs, suggesting that chronic alcohol exposure portends a chronically pro-inflammatory profile in these cells.
authors.affiliation: Department of Surgery, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Alcohol Research Program, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA.
authors.forename: Eileen Bock
authors.initials: EB
authors.lastname: O'Halloran
authors.affiliation: Department of Surgery, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Alcohol Research Program, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Curtis
authors.affiliation: Alcohol Research Program, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA.
authors.forename: Majid
authors.initials: M
authors.lastname: Afshar
authors.affiliation: Department of Surgery, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Alcohol Research Program, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Chen
authors.affiliation: Department of Surgery, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Alcohol Research Program, Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA; Loyola University, Chicago Stritch School of Medicine, 2160 S. 1st Ave., Maywood, IL 60153, USA. Electronic address: ekovacs@luc.edu.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, 13001 E. 17th Place, Aurora, CO 80045, USA.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Burnham
mesh_terms: D000328:Adult; D019973:Alcohol-Related Disorders / Q000378:metabolism*; D018893:Bronchoalveolar Lavage; D016022:Case-Control Studies; D002452:Cell Count; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators
keywords: AUD; Alveolar macrophage; Cytokine; Inflammation; Pulmonary