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

Our plain-English summary of Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development, by T.A. Brown, A. Holian, K.E. Pinkerton, et al (Inhalation Toxicology, 2016).

The study

• Authors: T.A. Brown, A. Holian, K.E. Pinkerton, J.W. Lee, Y.H. Cho
• Journal: Inhalation Toxicology
• Published: 2016;28(8):349-56
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory experiment in mice, not people. Pregnant mice breathed filtered air, tobacco smoke meant to mimic second-hand smoke during pregnancy, or that smoke during pregnancy and the pups' first 3 weeks. At 12 weeks, offspring in each group received Libby amphibole asbestos, or carrier liquid alone as a control, into the lungs. Some got one dose and were examined 24 hours later; others got four weekly doses and were checked for scarring. In filtered-air mice, a single asbestos dose raised signalling proteins IL-1b, TNF-a, IL-6 and IL-5. In both smoke groups, asbestos significantly raised IL-6 and IL-5, but not IL-1b or TNF-a, compared with filtered-air mice given no asbestos. Smoke exposure did not appear to add to changes in inflammatory cell counts 24 hours after asbestos. After repeated doses, collagen (a scarring marker) rose in all groups, significantly only in the two smoke groups. It was highest with smoke both before and after birth. The authors concluded that smoke exposure in the womb alters immune response and leads to greater disease after asbestos. They cited small sample sizes and urged caution.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment (mice exposed to tobacco smoke before and/or after birth, then to asbestos or a control liquid as adults)
• Who was studied: Offspring of pregnant C57BL/6 mice (4 dams exposed to filtered air, 8 to tobacco smoke). Smoke exposure took place at the University of California-Davis and asbestos work at the University of Montana. In each group, 24 pups were split into four subgroups of 6: asbestos or dispersion media, each given as either an acute or a chronic exposure. Dates are not given.
• Exposure: Environmental tobacco smoke at 1.0 mg/m3 of suspended particulates, 6 h/day, 7 days/week, during gestation, or during gestation plus 3 weeks after birth. At 12 weeks of age, mice received the respirable fraction of Libby 6-mix amphibole fibers, or dispersion media alone, by oropharyngeal aspiration. This was given either as a single dose (acute) or once a week for 4 weeks (chronic).
• Main results:
  • In filtered-air mice, a single asbestos dose significantly increased IL-1b, TNF-a, IL-6 and IL-5.
  • In both smoke-exposed groups, IL-6 and IL-5 after asbestos were significantly increased compared with the filtered-air, no-particle group. IL-1b and TNF-a were not significantly increased against that comparison.
  • At 24 hours after asbestos, asbestos increased neutrophil influx and decreased macrophage numbers. Smoke exposure had no additional effect on these measures.
  • After chronic asbestos exposure, collagen deposition increased in all three groups, but the increase was significant only in the prenatal and pre/postnatal smoke groups.
  • The pre/postnatal smoke group had the highest collagen deposition after chronic asbestos exposure.
  • Even without asbestos, the pre/postnatal smoke group showed areas of abnormal collagen deposition and lung structure.
• The authors' conclusion: The authors concluded that smoke exposure in the womb alters the immune response and leads to greater disease development after asbestos exposure. They added that this is made worse when smoke exposure continues during early development.
• Limitations the authors state:
  • Because of the small sample size, no significant effect on fiber clearance could be shown.
  • Females and males got the same asbestos dose, so females may have received a slightly higher dose relative to their lung size.
  • Females appeared more susceptible to asbestos, but this was not statistically significant because of the small sample size.
  • Measured cytokine levels in lavage fluid were relatively low, possibly because fibers bind cytokines. The authors said future work should confirm this with gene expression.
  • The authors urged caution in extrapolating the data and called for larger studies.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Cytokine, Collagen, Deposition, Asbestos Exposure.

Related studies

• Occupational exposures, environmental tobacco smoke, and lung cancer — F. Veglia, P. Vineis, et al. (2007)
• The effects of secondhand smoke exposure on HRCT findings among asbestos-exposed workers — T. Vierikko, R. Järvenpää, et al. (2008)
• Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice — A. Yamaguchi, T. Fujitani, et al. (2012)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma — M. Comar, N. Zanotta, et al. (2016)
• NHLBI workshop summary. Environmental lung diseases. Relationship between acute inflammatory responses to air pollutants and chronic lung disease — J. Crapo, F.J. Miller, et al. (1992)

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