Interleukin‐33 and alveolar macrophages contribute to the mechanisms underlying the exacerbation of IgE‐mediated airway inflammation and remodelling in mice

Summary Allergen‐specific IgE has long been regarded as a major molecular component of allergic asthma. Additionally, there is increasing evidence of the important roles of interleukin‐33 ( IL ‐33) in the disease. Here, we show that IL ‐33 and alveolar macrophages play essential roles in the exacerbation of IgE ‐mediated airway inflammation and remodelling. BALB /c mice passively sensitized with ovalbumin ( OVA )‐specific IgE monoclonal antibody ( mA b) were challenged with OVA seven times intratracheally. The seventh challenge exacerbated airway inflammation and remodelling compared with the fourth challenge; furthermore, markedly increased expression of IL ‐33 in the lungs was observed at the fourth and seventh challenges. When anti‐ IL ‐33 or anti‐ ST 2 antibody was administered during the fourth to seventh challenge, airway inflammation and remodelling were significantly inhibited at the seventh challenge. Because increases of IL ‐33 + and ST 2 + alveolar macrophages and ST 2 +   CD 4 + T cells in the lungs were observed at the fourth challenge, the roles of macrophages and CD 4 + cells were investigated. Depletion of macrophages by 2‐chloroadenosine during the fourth to seventh challenge suppressed airway inflammation and remodelling, and IL ‐33 production in the lung at the seventh challenge; additionally, anti‐ CD 4 mA b inhibited airway inflammation, but not airway remodelling and IL ‐33 production. Meanwhile, treatment with 2‐chloroadenosine or anti‐ CD 4 mA b decreased IL ‐33‐induced airway inflammation in normal mice; airway remodelling was repressed only by 2‐chloroadenosine. These results illustrate that macrophage‐derived IL ‐33 contributes to the exacerbation of IgE ‐mediated airway inflammation by mechanisms associated with macrophages and CD 4 + cells, and airway remodelling through the activation of macrophages.