Cannabinoids are components of the Cannabis sativa (marijuana) plant and are known to exert potent
anti-inflammatory, immunomodulatory, and analgesic effects through activation
of cannabinoid-1 and cannabinoid-2 (CB1 and CB2) receptors located in the central
nervous system (CNS) and immune cells, respectively. Cannabidiol (CBD) is the
main nonpsychotropic cannabinoid and reported to have beneficial effects in
many pathological conditions, including neuropsychiatric disorders and brain
inflammatory diseases, without having significant activity on CB1 and CB2
receptors.
Asthma is a disorder of the conducting airways, which contract too
much and too easily both spontaneously and in response to a wide range of
exogenous and endogenous stimuli. This airway hyper-responsiveness is
accompanied by enhanced sensory irritability of airways and increased mucus
secretion. Classically, asthma is characterized by chronic airway inflammation
and remodeling, hyper-responsiveness, and increase of T-helper cell 2 levels-
(Th2-) related cytokines.
Taking
a clue form various published results that CBD was shown to have potent
immunosuppressive and anti-inflammatory properties, researchers developed a
mouse model where they were able to prove protective effect of CBD upon
inflammatory response in an animal model of asthma. Researchers determined the
levels of 6 cytokines implicated in asthma, which can be divided by the
response profiles Th1 (TNF-α and IL-6) and Th2 (IL-4, IL-13, IL-10, and IL-5). Asthma
induction resulted in an increase in all cytokines levels when compared to
control animals. CBD treatment was able to decrease both Th1 and Th2 cytokines.
Study Design: Rats were immunized by an i.p.
injection of 10 µg of chicken ovalbumin (OVA) in 100 µL of aluminum hydroxide
(alum) or alum alone. After 14 days, rats were boosted with OVA or alum. Seven
days later, rats received aerosol challenges (30 min/for 3 days) with 1% OVA or
saline. CBD was suspended in 2% of polyoxyethylenesorbitan monooleate (Tween
80). The solutions were prepared immediately before use and were protected from
light during the experimental session. CBD was administered i.p. once a day during the last two days
of the OVA challenge at the dose of 5 mg/kg.
All
treatments were administered in a volume of 1 mL/kg of CBD or vehicle. For this
experiment, 21 rats were used, which were randomly divided into three groups:
vehicle (control) (n = 7), OVA + vehicle (asthma control) (n = 7), and OVA +
CBD (asthma + treatment) (n = 7). Blood samples were obtained 24 hours after
the last challenge by decapitation to determine the levels of cytokines.
Important clinical findings using a mice model:
1. CBD
treatment significantly decreased the levels of cytokines involved in the
immune response to an allergen, such as IL-4 and IL-5: IL-4 is responsible for
the inhibition of Th1 cells differentiation and for Th2 cells differentiation
and expansion and has an important role in IgE production. In addition, IL-4
seems to be a requisite for T lymphocytes to produce IL-5. IL-5 is essential
for the maturation of eosinophils, and it accumulates in the lung during the
inflammatory process of asthma.
2. IL-13
was reduced by CBD administration: IL-13 is considered a major stimulus for mucus
hypersecretion, an important characteristic of asthma, which contributes to the
exacerbation of symptoms.
3. CBD
is able to decrease IL-6 levels: IL-6 levels are increased in sputum and
systemic circulation in severe asthmatic patients, which can be responsible for
the raise of C-reactive protein circulation in these patients.
4. CBD
reduced the levels of TNF-α: TNF-α is a major mediator of severe asthma.
The
authors were also candid is pointing outs some limitations on their part in not
been able to measure lung function and the effect of CBD in bronchoalveolar
lavage fluid cytokines, but they are sure that these results can act as a guide
for future experiments.
Article citation: Dal-Pizzol, F.; et. al. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediators Inflamm 2015, 538670.
