title: Cigarette smoke enhances Th-2 driven airway inflammation and delays inhalational tolerance.
abstract: BACKGROUND
  Active smoking increases asthma severity and is related to diminished treatment efficacy. Animal models in which inhalation of both allergen and mainstream cigarette smoke are combined can help us to understand the complex interaction between both agents. We have recently shown that, in allergic mice, the airway inflammation can be cleared by repeated allergen challenge, resulting in the establishment of a state of inhalational tolerance.
  
  
  METHODS
  In this study, we assessed in vivo the impact of cigarette smoke on the efficacy and time course of this form of tolerance induction. We exposed sensitized mice to concurrent mainstream cigarette smoke and allergen (Ovalbumin- OVA) and measured the airway inflammation at different time points.
  
  
  RESULTS
  We first confirmed that aerosolized OVA administered for a prolonged time period (4-8 weeks) resulted in the establishment of tolerance. Concurrent OVA and smoke exposure for 2 weeks showed that tobacco smoke enhanced the Th-2 driven airway inflammation in the acute phase. In addition, the induction of the tolerance by repeated inhalational OVA challenge was delayed significantly by the tobacco smoke, since 4 weeks of concurrent exposure resulted in a more persistent eosinophilic airway inflammation, paralleled by a more mature dendritic cell phenotype. However, smoke exposure could not prevent the establishment of tolerance after 8 weeks of antigen exposure as shown by both histopathology (disappearance of the Th-2 driven inflammation) and by in vivo functional experiments. In these tolerized mice, some of the inflammatory responses to the smoke were even attenuated.
  
  
  CONCLUSIONS
  Cigarette smoke enhances acute allergic inflammation and delays, but does not abrogate the development of tolerance due to prolonged challenge with inhaled antigen in experimental asthma.
authors.affiliation: Department of Respiratory Diseases, Ghent University, Ghent, Belgium. chris.vanhove@ugent.be
authors.forename: Chris L
authors.initials: CL
authors.lastname: Van Hove
authors.forename: Katrien
authors.initials: K
authors.lastname: Moerloose
authors.forename: Tania
authors.initials: T
authors.lastname: Maes
authors.forename: Guy F
authors.initials: GF
authors.lastname: Joos
authors.forename: Kurt G
authors.initials: KG
authors.lastname: Tournoy
mesh_terms: D000818:Animals; D001991:Bronchitis / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D012906:Smoke; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D014026:Nicotiana
chemical_list: D018925:Chemokines; D016207:Cytokines; D012906:Smoke; D007073:Immunoglobulin E; D010047:Ovalbumin; C421864:hen egg lysozyme; D009113:Muramidase