Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on August 28, 2007; DOI: 10.1124/jpet.107.124719
0022-3565/07/3232-675-683$20.00
JPET 323:675-683, 2007
INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA
Modulation of Airway Responses to Influenza A/PR/8/34 by 
9-Tetrahydrocannabinol in C57BL/6 Mice
Departments of Pharmacology and Toxicology (J.P.B., N.E.K) and Pathobiology and Diagnostic Investigation (J.R.H., K.J.W.) and Center for Integrative Toxicology (J.P.B., P.W.F.K., J.R.H, N.E.K.), Michigan State University, East Lansing, Michigan
9-Tetrahydrocannabinol (9-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 9-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 9-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 9-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 9-THC treatment. Enumeration of inflammatory cell types in bronchoalveolar lavage fluid showed an attenuation of macrophages and CD4+ and CD8+ T cells in 9-THC-treated mice compared with controls. Likewise, the magnitude of inflammation and virus-induced mucous cell metaplasia, as assessed by histopathology, was reduced in 9-THC-treated mice by 10 dpi. Collectively, these results suggest that 9-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.
Received April 20, 2007; accepted August 27, 2007.
Address correspondence to: Dr. Norbert E. Kaminski, 315 National Food Safety and Toxicology Building, Michigan State University, East Lansing, MI 48824-1317. E-mail address: kamins11@msu.edu