Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: Role of CB1/CB2 receptors

Abstract

The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB1 and CB2 receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB1/2 receptors in this setting, we used pharmacological blockade of CBI and/or CB2 receptors by the selective antagonists and moreover CB1/CB2 receptor double-knockout mice (CB1-/-/CB2-/-) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB1/CB2 receptor-independent signalling seems likely in the observed results. (C) 2010 Elsevier GmbH. All rights reserved.