In utero exposure to environmental tobacco smoke potentiates adult responses to allergen in BALB/c mice.
BACKGROUND
Fetal stress has been linked to adult atherosclerosis, obesity, and diabetes. Epidemiology studies have associated fetal exposure to maternal smoking and postnatal exposure to environmental tobacco smoke (ETS) with increased asthma risk.


OBJECTIVE
We tested the hypothesis, in a mouse model of asthma, that in utero ETS exposure alters airway function and respiratory immune responses in adults.


METHODS
Pregnant Balb/c mice were exposed daily to ETS or HEPA-filtered air (AIR). Offspring inhaled aerosolized ovalbumin (OVA) or saline in weeks 7-8. Regardless of whether they inhaled OVA or saline, mice were sensitized by OVA injections in weeks 11 and 13 followed by OVA aerosol challenge in weeks 14-15. At three time points, we assessed OVA-specific serum immunoglobins, bronchoalveolar lavage cells and cytokines, lung and nasal histopathology, and airway hyperresponsiveness (AHR).


RESULTS
At 6 weeks, we found no significant differences between in utero ETS and AIR mice. At 10 weeks, following OVA aerosol, ETS mice displayed greater AHR than AIR mice (alpha = 0.05), unaccompanied by changes in histopathology, cytokine profile, or antibody levels. At 15 weeks, mice that had inhaled saline in weeks 7-8 developed airway inflammation: eosinophilia (alpha = 0.05), interleukin-5 (alpha = 0.05), and AHR (alpha = 0.05) were greater in ETS mice than in AIR mice. Mice that had inhaled OVA in weeks 7-8 demonstrated no airway inflammation after sensitization and challenge.


CONCLUSIONS
In utero ETS exposure exacerbates subsequent adult responses to initial allergen exposure.
Penn
Arthur L
AL
Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA. apenn@vetmed.lsu.edu
Rouse
Rodney L
RL
Horohov
David W
DW
Kearney
Michael T
MT
Paulsen
Daniel B
DB
Lomax
Larry
L
D000336:Aerosols; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D000917:Antibody Formation; D001249:Asthma / Q000209:etiology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000336:Aerosols; D000485:Allergens; D016207:Cytokines; D014028:Tobacco Smoke Pollution; D010047:Ovalbumin