title: Effects of 4 months of smoking in mice with ovalbumin-induced airway inflammation.
abstract: BACKGROUND
  The effects of smoking on asthma pathogenesis are complex and not well studied. We have shown recently that 3 weeks of smoking attenuates ovalbumin (OVA)-induced airway inflammation in mice and that 4-6 months of smoking induces emphysema in mice without airway inflammation. Effects of combined long-term smoking and OVA exposure have not been investigated so far.
  
  
  OBJECTIVE
  To study whether long-term smoking affects progression of allergic airway inflammation and/or enhances the development of emphysema in mice.
  
  
  METHODS
  Mice were sensitized to OVA and challenged with saline or OVA aerosols for 6 months. From 2 months onwards, mice were also exposed to air or smoke. Lung tissue was analysed for extent of inflammation, emphysema, remodelling and for cytokine levels, and serum for OVA-specific IgE levels.
  
  
  RESULTS
  Chronic OVA exposure of 6 months resulted in a T helper type 2 (Th2)-type inflammation with increased levels of IL-4, IL-5, IL-6 and infiltration of eosinophils, CD4(+) T cells, macrophages and plasma cells. Smoking induced a Th17-type of airway inflammation, characterized by neutrophils, macrophages, B cells and increased levels of IL-17, IL-6, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1. Concomittant smoking and OVA exposure resulted in inflammation similar to OVA exposure alone. OVA exposure increased IgE levels compared with saline exposure, and smoking did not further increase these levels.
  
  
  CONCLUSIONS
  We did not find evidence for increased inflammation, IgE levels or emphysema in mice with allergic airway inflammation after 4 months of smoking compared with non-smoking. However, a 4-month exposure to smoke alone did enhance neutrophilic airway inflammation characterized by high pulmonary IL-17 levels. A Th2 inflammatory environment due to OVA exposure may be one explanation as to why no further detrimental effects of smoking on allergic airway inflammation were found.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. BNMelgert@mac.com
authors.forename: B N
authors.initials: BN
authors.lastname: Melgert
authors.forename: W
authors.initials: W
authors.lastname: Timens
authors.forename: H A
authors.initials: HA
authors.lastname: Kerstjens
authors.forename: M
authors.initials: M
authors.lastname: Geerlings
authors.forename: M A
authors.initials: MA
authors.lastname: Luinge
authors.forename: J P
authors.initials: JP
authors.lastname: Schouten
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.forename: M N
authors.initials: MN
authors.lastname: Hylkema
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004646:Emphysema / Q000139:chemically induced / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology; D010047:Ovalbumin / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012906:Smoke; D013997:Time Factors
chemical_list: D016207:Cytokines; D012906:Smoke; D007073:Immunoglobulin E; D010047:Ovalbumin