Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor

Eur J Pharmacol. 2012 Mar 5;678(1-3):78-85. doi: 10.1016/j.ejphar.2011.12.043. Epub 2012 Jan 12.

Abstract

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use*
  • Bone Marrow Cells / drug effects
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cannabidiol / antagonists & inhibitors
  • Cannabidiol / pharmacology*
  • Cannabidiol / therapeutic use
  • Cannabinoids / pharmacology*
  • Cannabinoids / therapeutic use
  • Capillary Permeability / drug effects
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Leukocytes / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / metabolism
  • Receptor, Adenosine A2A / physiology*
  • Triazines / pharmacology
  • Triazoles / pharmacology

Substances

  • Adenosine A2 Receptor Antagonists
  • Anti-Inflammatory Agents
  • Cannabinoids
  • Chemokines
  • Cytokines
  • Receptor, Adenosine A2A
  • Triazines
  • Triazoles
  • ZM 241385
  • Cannabidiol
  • Peroxidase