PT  - JOURNAL ARTICLE
AU  - Buchweitz, John P.
AU  - Karmaus, Peer W. F.
AU  - Harkema, Jack R.
AU  - Williams, Kurt J.
AU  - Kaminski, Norbert E.
TI  - Modulation of Airway Responses to Influenza A/PR/8/34 by Δ<sup>9</sup>-Tetrahydrocannabinol in C57BL/6 Mice
AID  - 10.1124/jpet.107.124719
DP  - 2007 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 675--683
VI  - 323
IP  - 2
4099  - http://jpet.aspetjournals.org/content/323/2/675.short
4100  - http://jpet.aspetjournals.org/content/323/2/675.full
SO  - J Pharmacol Exp Ther2007 Nov 01; 323
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics