title: A study of the effect of proinflammatory cytokines on the epithelial cells of smokers, with or without COPD.
abstract: BACKGROUND
  Cigarette smoke is the main cause of inflammation in COPD. The mechanisms that differentiate smokers who develop COPD are diverse. In this study, we analyzed the presence of cytokines in the respiratory secretions of smokers with or without COPD and the secretory properties of the differentiated bronchial epithelium obtained from the individuals themselves after exposure to tobacco smoke.
  
  
  METHODS
  Twenty-seven smokers were studied, 12 of whom had COPD that had not been previously treated with steroids. In 11, samples were obtained by means of induced sputum, and the remaining samples were collected from bronchial aspiration after bronchoscopy. Concentrations of IL-8, IL-13 and TNFα in the supernatant were determined. The results obtained were compared between individuals with and without COPD, and we studied their relationship with the severity of COPD as expressed by the degree of obstruction, dyspnea, presence of hypersecretion and intensity of smoking. Bronchial epithelial cell cultures were obtained by air-liquid interface in 4 smokers. The samples were exposed to increasing concentrations of cigarette smoke (5-20%) and the epithelial mRNA expressions of MUC5AC, IL8 and TNFα were determined.
  
  
  RESULTS
  COPD patients had significantly higher values of IL-8 than healthy smokers (41 [22] vs. 21 [12] pM). The values of IL-8 correlated significantly with the severity of the obstruction (r=0.6; p<0.05), dyspnea (r=0.45; p<0.05) and the presence of hypersecretion. There was no relationship between cytokines and the intensity or duration of the tobacco habit. Cigarette smoke produced a dose-dependent increase in the expression of RNAm for Muc5AC, IL8 and TNFα.
  
  
  CONCLUSIONS
  There are differences in cytokine production (fundamentally IL8) between smokers and smokers with COPD which could be explained by the direct action of cigarette smoke on epithelial cells.
authors.affiliation: Hospital Universitari i Politècnic La Fe, Valencia, España. dediego_alf@gva.es
authors.forename: Alfredo De Diego
authors.initials: Ade D
authors.lastname: Damiá
authors.forename: Julio Cortijo
authors.initials: JC
authors.lastname: Gimeno
authors.forename: M José Selma
authors.initials: MJ
authors.lastname: Ferrer
authors.forename: Montserral León
authors.initials: ML
authors.lastname: Fabregas
authors.forename: Patricia Almudever
authors.initials: PA
authors.lastname: Folch
authors.forename: Javier Milara
authors.initials: JM
authors.lastname: Paya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D012907:Smoking / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines