title: Cigarette smoke impacts immune inflammatory responses to influenza in mice.
abstract: BACKGROUND
  Studies have shown that cigarette smoke impacts respiratory host defense mechanisms; however, it is poorly understood how these smoke-induced changes impact the overall ability of the host to deal with pathogenic agents.
  
  
  OBJECTIVE
  The objective of this study was to investigate the impact of mainstream cigarette smoke exposure on immune inflammatory responses and viral burden after respiratory infection with influenza A.
  
  
  METHODS
  C57BL/6 mice were sham- or smoke-exposed for 3 to 5 mo and infected with either 2.5 x 10(3) pfu (low dose) or 2.5 x 10(5) pfu (high dose) influenza virus.
  
  
  RESULTS
  Although smoke exposure attenuated the airway's inflammatory response to low-dose infection, we observed increased inflammation in smoke-exposed compared with sham-exposed mice after infection with high-dose influenza, despite a similar rate of viral clearance. The heightened inflammatory response was associated with increased expression of tumor necrosis factor-alpha, interleukin-6, and type 1 IFN in the airway, and increased mortality. Importantly, smoke exposure did not interfere with the development of influenza-specific memory responses; sham- and smoke-exposed animals were equally protected upon viral rechallenge.
  
  
  CONCLUSIONS
  Our study suggests that, in mice, cigarette smoke affects primary antiviral immune-inflammatory responses, whereas secondary immune protection remains intact.
authors.affiliation: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, ON, L8N 3Z5 Canada.
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Robbins
authors.forename: Carla M T
authors.initials: CM
authors.lastname: Bauer
authors.forename: Neda
authors.initials: N
authors.lastname: Vujicic
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Gaschler
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lichty
authors.forename: Earl G
authors.initials: EG
authors.lastname: Brown
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D009980:Influenza A virus; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D009195:Peroxidase / Q000032:analysis; D012907:Smoking / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019562:Viral Load
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase