Cigarette smoke enhances Th-2 driven airway inflammation and delays inhalational tolerance.
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.
Van Hove
Chris L
CL
Department of Respiratory Diseases, Ghent University, Ghent, Belgium. chris.vanhove@ugent.be
Moerloose
Katrien
K
Maes
Tania
T
Joos
Guy F
GF
Tournoy
Kurt G
KG
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
D018925:Chemokines; D016207:Cytokines; D012906:Smoke; D007073:Immunoglobulin E; D010047:Ovalbumin; C421864:hen egg lysozyme; D009113:Muramidase