| First Author | Karmaus PW | Year | 2013 |
| Journal | Toxicol Sci | Volume | 131 |
| Issue | 2 | Pages | 419-33 |
| PubMed ID | 23152191 | Mgi Jnum | J:194099 |
| Mgi Id | MGI:5470343 | Doi | 10.1093/toxsci/kfs315 |
| Citation | Karmaus PW, et al. (2013) Delta9-tetrahydrocannabinol impairs the inflammatory response to influenza infection: role of antigen-presenting cells and the cannabinoid receptors 1 and 2. Toxicol Sci 131(2):419-33 |
| abstractText | Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has potent immune modulatory properties and can impair pathogen-induced immune defenses, which in part have been attributed to ligation of the cannabinoid receptors 1 (CB(1)) and 2 (CB(2)). Most recently, dendritic cells (DC) were identified for their potential to enhance influenza-induced immunopathology in mice lacking CB(1) and CB(2) (CB(1) (-/-)CB(2) (-/-)). This study focused on the modulation of the inflammatory immune response to influenza by Delta(9)-THC and the role of CB(1) and/or CB(2) as receptor targets for Delta(9)-THC. C57Bl/6 (wild type) and CB(1) (-/-)CB(2) (-/-) mice were administered Delta(9)-THC (75 mg/kg) surrounding the intranasal instillation of A/PR/8/34 influenza virus. Three days post infection (dpi), Delta(9)-THC broadly decreased expression levels of mRNA induced by the innate immune response to influenza, suppressed the percentage of interferon-gamma (IFN-gamma)-producing CD4(+) and interleukin-17-producing NK1.1(+) cells, and reduced the influx of antigen-presenting cells (APC), including inflammatory myeloid cells and monocytes/macrophages, into the lung in a CB(1)- and/or CB(2)-dependent manner. Delta(9)-THC had little effect on the expression of CD86, major histocompatibility complex I (MHC I), and MHC II by APC isolated from the lung. In vitro studies demonstrated that lipopolysaccharide (LPS)-induced maturation was suppressed by Delta(9)-THC in bone marrow-derived DC (bmDC). Furthermore, antigen-specific IFN-gamma production by CD8(+) T cells after coculture was reduced by Delta(9)-THC treatment of bmDC in a CB(1)- and/or CB(2)-dependent manner. Collectively, these studies suggest that Delta(9)-THC potently suppresses myeloid cell immune function, in a manner involving CB(1) and/or CB(2), thereby impairing immune responses to influenza infection. |
