Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 310; no. 6; pp. L507 - L518
• Main Authors: Gaydos, Jeanette, McNally, Alicia, Guo, Ruixin, Vandivier, R. William, Simonian, Philip L., Burnham, Ellen L.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 15.03.2016
• Series: Translational Research in Acute Lung Injury and Pulmonary Fibrosis
• Subjects: Acetylcysteine - pharmacology; Adult; Alcoholism; Alcoholism - immunology; Alcoholism - metabolism; Antioxidants - pharmacology; Bronchoalveolar Lavage Fluid - immunology; Call for Papers; Case-Control Studies; Cells; Cells, Cultured; Female; Human subjects; Humans; Immune system; Inflammation Mediators - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lipopolysaccharides - pharmacology; Male; Middle Aged; Oxidative stress; Respiratory diseases; Smoking; Smoking - immunology; Smoking - metabolism; Teichoic Acids - pharmacology; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - metabolism; mononuclear cells; pathogen-associated molecular patterns; oxidative stress; smoking
• ISSN: 1040-0605; 1522-1504; 1522-1504
• DOI: 10.1152/ajplung.00242.2015

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.