Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

Abstract

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

• Asbestos
• environmental tobacco smoke
• fibrosis
• inflammation

Acknowledgements

The authors thank Pam Shaw, Lou Herritt, Mary Buford, Britten Postma, Virginia Kay, Melisa Schelvan (Center for Environmental Health Sciences at University of Montana), Dale Uyeminami and Shanie McCarty (Center for Health and the Environment at University of California, Davis) for their expert technical assistance with various aspects of this manuscript. We also thank the work of Dr Jack Harkema at Michigan State University, who reviewed and scored lung tissue sections of the ETS and asbestos-exposed mice as well as provided a summary of the observed histopathology.

Declaration of interest

No potential conflicts of interest were disclosed.

The National Institute of General Medical Sciences (P30 GM10333) and the National Institute of Environmental Health Sciences (R01 ES023209) supported this work. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NIGMS or NIEHS.