Asthma is an inflammatory disease of the lungs characterized by increased infiltration of leukocytes, especially eosinophils, into the airways, and reduced respiratory function. The inflammation leads to bronchoconstriction, increased airway hyperresponsiveness (AHR), and mucus production .
Resveratrol has been detected in trees, in a few flowering plants, in peanuts, and in grapevines. Numerous in vitro studies have described different biological effects of resveratrol (for review, see reference). The major properties of interest are the antioxidative, anti-inflammatory, and estrogenic effects, as well as anticancer and chemopreventative activities. Recently, resveratrol has been suggested to have many properties that could be beneficial in the treatment of several chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and arthriti. Although it was earlier reported that resveratrol reduced inflammatory mediators in COPD patients, in vivo demonstration of any anti-allergic or anti-asthmatic property of resveratrol was lacking. Here we demonstrate such properties, for the first time, using an OVA-induced mouse model of allergic asthma.
Before Meeyoung Lee investigating the effects of resveratrol (30 mg/kg) in a mouse model of allergic asthma, we studied preliminarily the dose effects of resveratrol (20, 30 and 50 mg/kg) on IgE, IgG, and IgG2a in serum to confirm the optimal dosages of resveratrol (data not shown). We used 30 mg/kg (similar to 50 mg/kg) of resveratrol because that dosage was most effective. In the present study we show that resveratrol (30 mg/kg) markedly reduced the AHR response to methacholine; significantly inhibited increases in total inflammatory cell counts and eosinophil counts in BALF induced by ovalbumin; reduced the levels of total IgE, OVA-specific IgE, IgG2a, IL-4, and IL-5 in serum and BALF; and substantially inhibited both OVA-induced eosinophilia in lung tissue and mucus hypersecretion by airway goblet cells.
In most cases, AHR is strongly associated with airway inflammation. AHR is a measure of the bronchial constriction commonly found in asthmatics. Our data show that resveratrol inhibited OVA-induced AHR caused by inhaled methacholine. IL-5 is a specific stimulator of eosinophil activation and is synthesized by Th2 lymphocytes, mast cells, and eosinophils. It has been established that IL-5-mediated eosinophilia contributes to AHR by generating cytotoxic products, such as major basic protein (MBP), eosinophilic cationic protein (ECP), and other lipid mediators, including platelet activated factor (PAF) and cysteinyl-leukotrienes, which lead to tissue damage. Th2 lymphocytes play an important role in the initiation and progression of allergic diseases, including asthma, by releasing IL-4, IL-5, and IL-13. These Th2 cytokines induce inflammatory responses, such as airway infiltration and eosinophil activation, IgE production, and mucus secretion. In the knockout murine model, these cytokines have been implicated in the processes of sensitization and allergic responsiveness, causing increases in IgE levels, and eosinophilia into the airways. The presence of increased numbers of BALF eosinophils is a hallmark of asthma. We found that, compared with PBS-treated mice, resveratrol-treated mice had significantly reduced lung eosinophilia in BALF and lung tissue. This effect of resveratrol treatment may result from a decrease in the levels of Th2 cytokines responsible for eosinophil recruitment into the lung in asthma. IgE, together with IgG1, has been closely associated with Th2-type responses, whereas IgG2a has been allied to Th1-type responses. Oral administration of resveratrol to OVA-sensitized/challenged mice significantly decreased serum IgE levels and IgG2a levels, but had no effect on overall IgG levels. Our present results show that oral administration of resveratrol inhibited IgE production and increased IgG2a levels in serum. These effects could be related to the induction of Th1-type IL-12 and IFN-γ production, and inhibition of Th2-related IL-5 and IL-13 synthesis. In this study, resveratrol significantly reduced the levels of total IgE, OVA-specific IgE, IgG2a, IL-4, and IL-5 in plasma and BALF in an OVA-induced asthmatic mouse model.
These results provide further evidence that oral administration of resveratrol is suitable for treatment of allergic diseases such as asthma.
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