Allergic inflammation (AI). Allergic diseases, including asthma/allergic airway inflammation (AAI), allergic rhinitis, atopic dermatitis and food allergy affecting ~20% of the global population are continually increasing. These are all chronic inflammatory processes, characterised by IgEmediated mast cell (MCs) activation through the FcεRI bound allergen and subsequent eosinophil (Eos) infiltration.
Most of the allergic disease patients’ symptoms are controlled by either symptomatic drugs or corticosteroids. Nevertheless, some patients, such as those suffering of severe asthma, are usually steroid-resistant and therefore allergic disease such as severe asthma and atopic dermatitis have been labelled as unmet clinical needs by the WHO.
As CBD has been shown to be a potent anti-inflammatory agent and to affect asthma in rodent models we will examine whether our test compound also affects this disease and whether MCs and Eos are directly influenced by it. Since MCs and Eos are the main effector in AAI, we will examine the direct effect of cannabinoids on these two cell types; MCs and Eos.
In asthma as in the other allergic diseases, MCs release inflammatory mediators to orchestrate the immediate-early phase of the response that is usually followed by a late phase response characterized by the recruitment and activation of several inflammatory cells, and notably by the Eos (bone marrow-derived, blood resident granulocytes that respond to MC-released mediators and appear to play pivotal roles in the nature and extent of airway inflammatory responses together with other innate and adaptive immune cells. When MCs and Eos are activated, several preformed (e.g.histamine from MCs, granular basic mediators from Eos) and newly synthesized (e.g., lipid) mediators and cytokines/chemokines are released. Both Eos and MCs have a “lead” role in allergic reactions, but are also involved in host-defence responses, cancer autoimmune diseases and tissue repair/fibrosis and pro-angiogenic processes.
Following the completion of these experiments we will know whether our cannabinoid will affect the AAI and whether it has the potential to directly down regulate the pro-inflammatory functions of MCs and Eos
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