Suppression of pulmonary innate host defence in smokers

• Published in: Thorax Vol. 64; no. 2; pp. 144 - 149
• Main Authors: Herr, C, Beisswenger, C, Hess, C, Kandler, K, Suttorp, N, Welte, T, Schroeder, J-M, Vogelmeier, C, Group, R Bals for the CAPNETZ Study
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.02.2009; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Antimicrobial agents; Bacteria; beta-Defensins - metabolism; Biological and medical sciences; Cardiology. Vascular system; Chronic obstructive pulmonary disease; Cigarettes; Community-Acquired Infections - immunology; Defense; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - immunology; Epithelial Cells - microbiology; Experiments; Female; Humans; Hydrogen Peroxide - pharmacology; Immune Tolerance - immunology; Immunity, Innate - immunology; Immunity, Mucosal - immunology; Infections; Male; Medical sciences; Middle Aged; Oxidants - pharmacology; Peptides; Pharynx - chemistry; Pneumology; Pneumonia; Pneumonia, Bacterial - immunology; Polyclonal antibodies; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa - isolation & purification; Pseudomonas Infections - immunology; Smoking; Smoking - immunology; Sputum - chemistry; Tobacco, tobacco smoking; Toxicology; California; United Kingdom > UK; United States > US; Germany; Human; Smoker; Lung; Suppression; Tobacco smoking; Anesthesia; Circulatory system; Cardiology
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thx.2008.102681

Background:Smoking increases the susceptibility to pulmonary infection and is a risk factor for the development of chronic obstructive pulmonary disease (COPD). It is postulated that cigarette smoke suppresses the activation of the innate immune system in response to bacterial infection.Methods:Using sensitive ex vivo analysis, the level of the endogenous antibiotic peptide human β-defensin-2 (hBD-2) was measured in pharyngeal washing fluid and sputum from patients with community acquired pneumonia. The regulation of antibacterial host defence molecules was studied in vitro. The effect of cigarette smoke on the antibacterial activity of differentiated airway epithelium and the expression of host defence molecules was studied in an in vitro infection model.Results:Current or former smoking was associated with significantly reduced hBD-2 levels in pharyngeal washing fluid and sputum from patients with acute pneumonia. Exposure of airway epithelium to smoke in vitro inhibited the induction of hBD-2 by bacteria. This correlated with decreased antimicrobial activity. This effect was mimicked by hydrogen peroxide, and catalase blunted the smoke-induced inhibition of epithelial host defence.Conclusions:Smoke exposure suppresses the induction of epithelial antibacterial host defences. These findings link smoking with increased susceptibility to infection. This mechanism may be important in the pathogenesis of pneumonia and COPD.