title: Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells.
abstract: Alcohol use disorders (AUDs) and tobacco smoking are associated with an increased predisposition for community-acquired pneumonia and the acute respiratory distress syndrome. Mechanisms are incompletely established but may include alterations in response to pathogens by immune cells, including alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs). We sought to determine the relationship of AUDs and smoking to expression of IFNγ, IL-1β, IL-6, and TNFα by AMs and PBMCs from human subjects after stimulation with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). AMs and PBMCs from healthy subjects with AUDs and controls, matched on smoking, were cultured with LPS (1 μg/ml) or LTA (5 μg/ml) in the presence and absence of the antioxidant precursor N-acetylcysteine (10 mM). Cytokines were measured in cell culture supernatants. Expression of IFNγ, IL-1β, IL-6, and TNFα in AMs and PBMCs was significantly increased in response to stimulation with LPS and LTA. AUDs were associated with augmented production of proinflammatory cytokines, particularly IFNγ and IL-1β, by AMs and PBMCs in response to LPS. Smoking diminished the impact of AUDs on AM cytokine expression. Expression of basal AM and PBMC Toll-like receptors-2 and -4 was not clearly related to differences in cytokine expression; however, addition of N-acetylcysteine with LPS or LTA led to diminished AM and PBMC cytokine secretion, especially among current smokers. Our findings suggest that AM and PBMC immune cell responses to LPS and LTA are influenced by AUDs and smoking through mechanisms that may include alterations in cellular oxidative stress.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado;
authors.forename: Jeanette
authors.initials: J
authors.lastname: Gaydos
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado;
authors.forename: Alicia
authors.initials: A
authors.lastname: McNally
authors.affiliation: Department of Biostatistics and Informatics, University of Colorado School of Public Health, Denver, Colorado; and.
authors.forename: Ruixin
authors.initials: R
authors.lastname: Guo
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado;
authors.forename: R William
authors.initials: RW
authors.lastname: Vandivier
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado; Division of Allergy and Immunology, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Simonian
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado; ellen.burnham@ucdenver.edu.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Burnham
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D000437:Alcoholism / Q000276:immunology* / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000276:immunology* / Q000378:metabolism; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C009900:lipoteichoic acid; D000111:Acetylcysteine
keywords: mononuclear cells; oxidative stress; pathogen-associated molecular patterns; smoking