Due to climate change, wildfires have increased in intensity and duration. While wildfires threaten lives directly, the smoke has more far-reaching adverse health impacts. During an extreme 2017 wildfire event, residents of Seeley Lake, Montana were exposed to unusually high levels of wood smoke (WS) causing sustained effects on lung function (decreased FEV 1 /FVC). Objective : The present study utilized an animal model of WS exposure to research cellular and molecular mechanisms of the resulting health effects. Methods : Mice were exposed to inhaled WS utilizing locally harvested wood to recapitulate community exposures. WS was generated at a rate resulting in a 5 mg/m 3 PM 2.5 exposure for five days. Results : This exposure resulted in a similar 0.28 mg/m 2 particle deposition (lung surface area) in mice that was calculated for human exposure. As with the community observations, there was a significant effect on lung function, increased resistance, and decreased compliance, that was more pronounced in males at an extended (2 months) timepoint and males were more affected than females: ex vivo assays illustrated changes to alveolar macrophage functions (increased TNFα secretion and decreased efferocytosis). Female mice had significantly elevated IL-33 levels in lungs, however, pretreatment of male mice with IL-33 resulted in an abrogation of the observed WS effects, suggesting a dose-dependent role of IL-33. Additionally, there were greater immunotoxic effects in male mice. Discussion : These findings replicated the outcomes in humans and suggest that IL-33 is involved in a mechanism of the adverse effects of WS exposures that inform on potential sex differences.
Keyphrases
- lung function
- air pollution
- cystic fibrosis
- climate change
- particulate matter
- healthcare
- chronic obstructive pulmonary disease
- high fat diet induced
- mental health
- mouse model
- endothelial cells
- public health
- rheumatoid arthritis
- type diabetes
- human health
- emergency department
- adipose tissue
- high throughput
- heavy metals
- high intensity
- weight loss
- oxidative stress
- adverse drug
- risk assessment
- high glucose
- induced pluripotent stem cells
- skeletal muscle
- glycemic control