Cigarette smoke exposure facilitates allergic sensitization in mice.
BACKGROUND
Active and passive smoking are considered as risk factors for asthma development. The mechanisms involved are currently unexplained.


OBJECTIVE
The aim of this study was to determine if cigarette smoke exposure could facilitate primary allergic sensitization.


METHODS
BALB/c mice were exposed to aerosolized ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung function tests were performed after the last exposure. The natural history and the immune memory of allergic sensitization were studied with in vivo recall experiments.


RESULTS
Exposure to OVA induced a small increase in OVA-specific serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory reaction was observed in the airways. Exposure to cigarette smoke did not induce IgE, but was characterized by a small but significant neutrophilic inflammatory reaction. Combining OVA with cigarette smoke not only induced a significant increase in OVA-specific IgE but also a distinct eosinophil and goblet cell enriched airway inflammation albeit that airway hyperresponsiveness was not evidenced. FACS analysis showed in these mice increases in dendritic cells (DC) and CD4+ T-lymphocytes along with a marked increase in IL-5 measured in the supernatant of lymph node cell cultures. Immune memory experiments evidenced the transient nature of these phenomena.


CONCLUSIONS
In this study we show that mainstream cigarette smoke temporary disrupts the normal lung homeostatic tolerance to innocuous inhaled allergens, thereby inducing primary allergic sensitization. This is characterized not only by the development of persistent IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory reaction.
Moerloose
Katrien B
KB
Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium. katrien.moerloose@ugent.be
Robays
Lander J
LJ
Maes
Tania
T
Brusselle
Guy G
GG
Tournoy
Kurt G
KG
Joos
Guy F
GF
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000485:Allergens; D014028:Tobacco Smoke Pollution; D007073:Immunoglobulin E