Modulation of airway responses to influenza A/PR/8/34 by Delta9-tetrahydrocannabinol in C57BL/6 mice.
Delta(9)-tetrahydrocannabinol (Delta(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 Delta(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 Delta(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 Delta(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 Delta(9)-THC treatment. Enumeration of inflammatory cell types in bronchoalveolar lavage fluid showed an attenuation of macrophages and CD4(+) and CD8(+) T cells in Delta(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 Delta(9)-THC-treated mice by 10 dpi. Collectively, these results suggest that Delta(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.
Buchweitz
John P
JP
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824-1317, USA.
Karmaus
Peer W F
PW
Harkema
Jack R
JR
Williams
Kurt J
KJ
Kaminski
Norbert E
NE
D000818:Animals; D053148:Caspase 3 / Q000235:genetics; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D006389:Hemagglutinins, Viral / Q000032:analysis; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055271:Mucin 5AC; D009077:Mucins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
D006389:Hemagglutinins, Viral; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger; D013759:Dronabinol; D053148:Caspase 3