Modulation of Airway Responses to Influenza A/PR/8/34 by Δ⁹-Tetrahydrocannabinol in C57BL/6 Mice

Abstract

⌬ 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 ϩ and CD8 ϩ 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 ϩ and CD8 ϩ T cells, to the lung.

Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Virus Infection in a Murine Model

“…Little is known about the role of IL-17 in viral pulmonary infections; it has been suggested that an IL-17 receptor agonist antagonizes the response to influenza virus challenge (12), but our results and those of others (22,50) indicate that Th17 cells can be involved in protection against influenza virus. Whereas other studies using immunosuppressive agents report exacerbated influenza disease (7,46), in this study, CT-treated mice appeared to develop initial Th1/Th17 inflammatory responses that directly contributed to enhanced survival. In our experiments, the viral challenge was given 24 h after immunomodulator administration.…”

“…However, immunomodulation does not always result in beneficial responses to infection. Administration of ⌬ 9 -THC, an immunosuppressive compound, decreased cellular infiltration and increased viral load when given prior to and during influenza virus infection (7). Similarly, sphingosine 1-phosphate (S1P) analog, an immunotherapeutic agent, was found to suppress induction of T-cell responses to influenza virus (46).…”

Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

“…The lungs were removed, formalin fixed, and paraffin embedded for hematoxylin and eosin (H&E) staining according to standard methods. Inflammatory changes on the basis of numbers of inflammatory cells and tissue damage in the lungs were determined by histology from H&E-stained longitudinal cross-sections and graded as no change (score ϭ 0), mild (score ϭ 1), moderate (score ϭ 2), or severe (score ϭ 3) as previously described (2). Sections were reviewed and scored in a blind fashion by a pathologist (C.-C.L.).…”

Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways

“…The images were analyzed by use of an inverted microscope (Olympus, Japan). Lung pathology was assessed by the histopathological scoring system as previously described (3,54).…”