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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.

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{at}msu.edu

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