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Arthur L. Penn,¹ Rodney L. Rouse,¹ David W. Horohov,² Michael T. Kearney,³ Daniel B. Paulsen,³ and Larry Lomax³

¹Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA; ²University of Kentucky, College of Agriculture, Lexington, Kentucky, USA; ³Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA

Abstract
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 (α = 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 (α = 0.05) , interleukin-5 (α = 0.05) , and AHR (α = 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.

Conclusion: In utero ETS exposure exacerbates subsequent adult responses to initial allergen exposure.

Key words: airway hyperresponsiveness, allergens, asthma, environmental tobacco smoke (ETS) , in utero, tolerance. Environ Health Perspect 115:548–555 (2007) . doi:10.1289/ehp.9780 available via http://dx.doi.org/ [Online 4 January 2007]

Address correspondence to A. Penn, CBS, LSU School of Veterinary Medicine, Skip Bertman Dr., Baton Rouge, LA 70803 USA. Telephone: (225) 578-9760. Fax: (225) 578-9895. E-mail: apenn@vetmed.lsu.edu

We thank T. Ahlert, M. Boudreaux, M. Faubion, and B. LaGroue for their technical assistance.

This study received support from the Louisiana Governor's Biotechnology Initiative.

A.P. received an honorarium from the Buxco Corp. in May 2006. The other authors declare they have no competing financial interests.

Received 2 October 2006 ; accepted 4 January 2007.