The role of eosinophils as effector cells in asthma pathogenesis has been questioned since an anti-interleukin (IL)-5 monoclonal antibody (mepolizumab), which depleted blood and sputum eosinophils, failed to inhibit allergen-induced bronchoconstriction and airway hyperresponsiveness. However, the effect of IL-5 blockade on tissue eosinophils was not examined. We sought to determine whether mepolizumab depletes airway tissue eosinophils and their products. Twenty-four patients with mild asthma received three intravenous doses of either 750 mg of mepolizumab or placebo in a randomized, double-blind, parallel-group fashion over 20 weeks. Mepolizumab produced a median decrease from baseline of 55% for airway eosinophils (interquartile range, 29-89%; p = 0.009 versus placebo), 52% for bone marrow eosinophils (45-76%, p = 0.003), and 100% for blood eosinophils (range, 67-100%, p = 0.02). Mepolizumab had no appreciable effect on bronchial mucosal staining of eosinophil major basic protein. There were no significant changes in clinical measures of asthma (airway hyperresponsiveness, FEV1, and peak flow recordings) between the mepolizumab and placebo-treated groups. Anti-IL-5 treatment reduces but does not deplete airway or bone marrow eosinophils. The role of the eosinophil remains uncertain. Further clinical studies in asthma with more effective antieosinophil strategies are required.

Eosinophil-derived TGF-β has been implicated in remodeling events in asthma. We hypothesized that reduction of bronchial mucosal eosinophils with anti–IL-5 would reduce markers of airway remodeling. Bronchial biopsies were obtained before and after three infusions of a humanized, anti–IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. The thickness and density of tenascin, lumican, and procollagen III in the reticular basement membrane (RBM) were quantified immunohistochemically by confocal microscopy. Expression of TGF-β1 mRNA by airway eosinophils was assessed by in situ hybridization, and TGF-β1 protein was measured in bronchoalveolar lavage (BAL) fluid by ELISA. At baseline, airway eosinophil infiltration and ECM protein deposition was increased in the RBM of asthmatics compared with nonasthmatic controls. Treating asthmatics with anti–IL-5 antibody, which specifically decreased airway eosinophil numbers, significantly reduced the expression of tenascin, lumican, and procollagen III in the bronchial mucosal RBM when compared with placebo. In addition, anti–IL-5 treatment was associated with a significant reduction in the numbers and percentage of airway eosinophils expressing mRNA for TGF-β1 and the concentration of TGF-β1 in BAL fluid. Therefore eosinophils may contribute to tissue remodeling processes in asthma by regulating the deposition of ECM proteins

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

This review will describe the structure and function of the eosinophil. The roles of several relevant cell surface molecules and receptors will be discussed. We will also explore the systemic and local processes triggering eosinophil differentiation, maturation, and migration to the lungs in asthma, as well as the cytokine-mediated pathways that result in eosinophil activation and degranulation, i.e., the release of multiple pro-inflammatory substances from eosinophil-specific granules, including cationic proteins, cytokines, chemokines growth factors, and enzymes. We will discuss the current understanding of the roles that eosinophils play in key asthma processes such as airway hyperresponsiveness, mucus hypersecretion, and airway remodeling, in addition to the evidence relating to eosinophil–pathogen interactions within the lungs.

No abstract

Eosinophil-derived TGF-β has been implicated in remodeling events in asthma. We hypothesized that reduction of bronchial mucosal eosinophils with anti-IL-5 would reduce markers of airway remodeling. Bronchial biopsies were obtained before and after three infusions of a humanized, anti-IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. The thickness and density of tenascin, lumican, and procollagen III in the reticular basement membrane (RBM) were quantified immunohistochemically by confocal microscopy. Expression of TGF-β1 mRNA by airway eosinophils was assessed by in situ hybridization, and TGF-β1 protein was measured in bronchoalveolar lavage (BAL) fluid by ELISA. At baseline, airway eosinophil infiltration and ECM protein deposition was increased in the RBM of asthmatics compared with nonasthmatic controls. Treating asthmatics with anti-IL-5 antibody, which specifically decreased airway eosinophil numbers, significantly reduced the expression of tenascin, lumican, and procollagen III in the bronchial mucosal RBM when compared with placebo. In addition, anti-IL-5 treatment was associated with a significant reduction in the numbers and percentage of airway eosinophils expressing mRNA for TGF-β1 and the concentration of TGF-β1 in BAL fluid. Therefore eosinophils may contribute to tissue remodeling processes in asthma by regulating the deposition of ECM proteins.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.