Abstract
BackgroundThalidomide is known to have anti-inflammatory and immunomodulatory actions. However, the effect and the anti-asthmatic mechanism of thalidomide in the pathogenesis of asthmatic airways are not fully understood.ObjectiveThis study is designed to determine the effect and the potential mechanism of thalidomide in the pathogenesis of asthmatic airways using animal model of allergic asthma.MethodsSix-week-old female BALB/C mice were sensitized with alum plus ovalbumin (OVA) and were exposed to OVA via intranasal route for 3 days for challenge. Thalidomide 200 mg/kg was given via gavage twice a day from a day before the challenge and airway hyperresponsivenss (AHR), airway inflammatory cells, and cytokines in bronchoalveolar lavage fluids (BALF) were evaluated. The expression levels of pro-inflammatory cytokines and other mediators were evaluated using ELISA, real time (RT)-qPCR, and flow cytometry. CRL-2456, alveolar macrophage cell line, was used to test the direct effect of thalidomide on the activation of macrophages in vitro.ResultsThe mice with thalidomide treatment showed significantly reduced levels of allergen-induced BALF and lung inflammation, AHR, and the expression of a number of pro-inflammatory cytokines and mediators including Th2 related, IL-17 cytokines, and altered levels of allergen-specific IgG1/IgG2a. Of interesting note, thalidomide treatment significantly reduced expression levels of allergen- or Th2 cytokine-stimulated alternative activation of macrophages in vivo and in vitro.ConclusionThese studies highlight a potential use of thalidomide in the treatment of allergic diseases including asthma. This study further identified a novel inhibitory effect of thalidomide on alternative activation of macrophages as a potential mechanism of anti-asthmatic effect of thalidomide.
Highlights
Allergic asthma is a chronic inflammatory disease of the airways
This study further identified a novel inhibitory effect of thalidomide on alternative activation of macrophages as a potential mechanism of anti-asthmatic effect of thalidomide
We demonstrated that thalidomide treatment before and after each challenge with ovalbumin (OVA) almost completely suppressed allergen-induced eosinophil-dominant airway inflammation, airway hyper-responsiveness (AHR), and Th2-deriven humoral responses in OVA-sensitized mice
Summary
Allergic asthma is a chronic inflammatory disease of the airways It is characterized by pulmonary eosinophilia, mucus hypersecretion, an increase in serum levels of allergen-specific IgE, and airway hyper-responsiveness (AHR) and Th2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13 [1,2,3,4,5]. The Th2 cytokine profile in asthmatic lung contributes to the appearance of alternatively activated or M2 macrophages. These macrophages generate several proallergic factors, such as chemokines, chitinase-like molecules [6] and ‘found in inflammatory zone 1’(FIZZ1, known as Relm-α) [7,8], which all contribute to the airway inflammatory and remodeling responses during asthma [9,10]. The effect and the anti-asthmatic mechanism of thalidomide in the pathogenesis of asthmatic airways are not fully understood.
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