Abstract
Δ9-Tetrahydrocannabinol (Δ9-THC) has been widely established as a modulator of host immune responses. Accordingly, the objective of the present study was to examine the effects of Δ9-THC on the immune response within the lungs and associated changes in the morphology of the bronchiolar epithelium after one challenge with a nonlethal dose of the influenza virus A/PR/8 (PR8). C57BL/6 mice were treated by oral gavage with Δ9-THC and/or vehicle (corn oil) for 5 consecutive days. On day 3, mice were instilled intranasally with 50 plaque-forming units of PR8 and/or vehicle (saline) 4 h before Δ9-THC exposure. Mice were subsequently killed 7 and 10 days postinfection (dpi). Viral hemagglutinin 1 (H1) mRNA levels in the lungs were increased in a dose-dependent manner with Δ9-THC treatment. Enumeration of inflammatory cell types in bronchoalveolar lavage fluid showed an attenuation of macrophages and CD4+ and CD8+ T cells in Δ9-THC-treated mice compared with controls. Likewise, the magnitude of inflammation and virus-induced mucous cell metaplasia, as assessed by histopathology, was reduced in Δ9-THC-treated mice by 10 dpi. Collectively, these results suggest that Δ9-THC treatment increased viral load, as assessed by H1 mRNA levels, through a decrease in recruitment of macrophages and lymphocytes, particularly CD4+ and CD8+ T cells, to the lung.
Footnotes
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This work was supported by a Michigan State University Foundation strategic partnership grant, National Institutes of Health Grant DA07908, and the National Institute of Environmental Health Sciences Training Grant T32 ES07255.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.124719.
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ABBREVIATIONS: IFN, interferon; Δ9-THC, Δ9-tetrahydrocannabinol; BALF, bronchoalveolar lavage fluid; H1, hemagglutinin 1; dpi, days postinfection; PR8, influenza A/PR/8/34; PCR, polymerase chain reaction; CAS-3, caspase-3; IL, interleukin; MCP, monocyte chemoattractant protein; TNF, tumor necrosis factor; PE, phycoerythrin; ANOVA, analysis of variance.
- Received April 20, 2007.
- Accepted August 27, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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Modulation of Airway Responses to Influenza A/PR/8/34 by Δ9-Tetrahydrocannabinol in C57BL/6 Mice
