Cannabis is widely used for recreational and medicinal purposes. Inhalation of cannabis smoke is the predominant method of drug consumption, exposing the lungs to THC and CBD, as well as a plethora of toxic combustion products. Clinical observations suggest that cannabis smoking contributes to the development of respiratory symptoms and may play a role in the pathogenesis of inflammatory lung disease. However, the association between cannabis smoke, dysregulated pulmonary immunity, and the development of lung disease is inconclusive. To improve our understanding of this relationship, we developed novel mouse models to investigate the effect of cannabis smoke exposure on lung immunity.
Using compositionally relevant cannabis strains, we established a mouse model of cannabis smoke exposure and validated that it delivers cannabis smoke by measuring cannabis smoke-associated metabolites in the blood. In our initial lung immune characterization, we demonstrated that acute cannabis smoke exposure induces modest changes to innate immune cellularity in the airways and lung tissue. Specifically, lung macrophage subpopulations were proportionally altered following smoke exposure. As well, we demonstrated that lung disease-associated mediators, including MDC, TARC, and VEGF, were dysregulated in cannabis smoke-exposed lung tissue.
In addition to our initial characterization, we established a first-of-its-kind concurrent cannabis smoke exposure and influenza infection model. Using this model, we demonstrated that cannabis smoke exposure exacerbates weight loss following influenza infection. These increases in weight loss corresponded with dysregulated cellular responses and immune mediator expression. Cell types involved in early innate immune signaling, such as macrophages and dendritic cells, were significantly affected by concurrent exposure and infection. Additionally, anti-viral mediators. including IFNγ, IP-10, RANTES, and TNFα, were decreased in cannabis smoke-exposed, infected lung tissue.
Collectively, we defined two novel models of cannabis smoke exposure that can be leveraged in future investigations on the inflammatory effects and associated health outcomes of cannabis smoke. / Thesis / Master of Science (MSc) / Cannabis is widely used for recreational and medical purposes. Smoking is the most popular method to consume the drug among users. However, little is understood about the effects of cannabis smoke on lung health, despite evidence suggesting that it may lead to negative health outcomes. To address this gap in knowledge, we developed two unique mouse models of cannabis smoke exposure. Using these models, we explored the effects of cannabis smoke on lung immune responses in healthy and influenza infected mice. Our findings suggested that lung immunity is altered following cannabis smoke exposure. Additionally, we found that overall health was worsened during influenza infection in cannabis smoke-exposed mice. This effect was associated with weakened viral immunity in the lungs. The models we developed and the findings using it thus far create the foundation for future studies on cannabis smoke and lung health.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/26644 |
| Date | January 2021 |
| Creators | Fantauzzi, Matthew |
| Contributors | Hirota, Jeremy, Medical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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