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.

Keywords: Asbestos; environmental tobacco smoke; fibrosis; inflammation.

Figure 1. A model showing ETS and asbestos exposures

Group 1: FA, Group 2: prenatal ETS, Group 3: pre/postnatal ETS exposed to asbestos at 12 weeks of age. WLL fluid was collected 24 hr after exposure for the acute study. Mice in the chronic study were exposed to asbestos once per week for an additional three weeks. One month later lung tissue was collected for histological analysis.

Figure 2. Inflammatory cytokine release for FA, prenatal, and pre/postnatal ETS-exposed mice in WLL after 24 hr asbestos exposure

Alteration in level of (A) IL-1β, (B) TNF-α, (C) IL-6, (D) IL-5, (E) KC/GRO, and (F) IL-10. Data are expressed as mean ± SEM. Asterisks indicate significance ** at P < 0.01, * at P < 0.05 compared to FA, no particle. n = 6 mice per condition.

Figure 3. Inflammatory cell infiltration for FA, prenatal, and pre/postnatal ETS-exposed mice in WLL after 24 hr asbestos exposure

(A) Total cell numbers, (B) macrophages, and (C) neutrophils. Data expressed as mean ± SEM. Asterisks indicate significance, ** at P < 0.01, * at P < 0.05 compared to FA, no particle. n = 6 mice per condition.

Figure 4. Collagen deposition in ETS- and asbestos-exposed mice

Representative pictures of interstitial histology for each group.

Figure 5. Collagen deposition for FA, prenatal and pre/postnatal ETS-exposed mice after chronic asbestos exposure

Asbestos exposure leads to a significant increase in collagen deposition for ETS groups, and the pre/postnatal ETS group appeared to have the highest level of abnormal lung pathology. Data expressed as mean ± SEM. Asterisks indicate significance *** at P < 0.001, ** at P <0.01 compared to FA, no particle. n = 3 mice per condition.