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INTRODUCTION

Eosinophils cause lung disease when they release granule proteins, cytokines, arachidonic acid metabolites, superoxide anions, and metalloproteases and other mediators that cause tissue damage, lead to bronchial hyperresponsiveness, and further activate immunologic cascades that enhance inflammation. Pulmonary eosinophilia is a result of enhanced eosinophil development through eosinophil-lineage commitment and maturation in the bone marrow, recruitment into the lung from the circulation, and prolonged eosinophil survival.

Interleukin 5 (IL-5) is the primary cytokine responsible for eosinophilia. While not absolutely essential for eosinophil development, IL-5 enhances eosinophil development and function by stimulating eosinophil differentiation, proliferation, and maturation in the bone marrow, as well as tissue recruitment, activation, and survival. In addition to IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-33 have lesser but important effects on eosinophil differentiation, maturation, and activation.1 IL-5 acts by binding to IL-5 receptor alpha and signaling through a heterodimeric type 1 cytokine receptor composed of the alpha and beta chain. IL-5 receptors are predominantly expressed on eosinophils, but also on some basophils and B cell precursors.2 The importance of IL-5 in eosinophilic diseases was tested in animal models using mice with deletion of the IL-5 gene. These animals had marked reductions in eosinophil development, circulation, and recruitment, and absent eosinophil damage in tissues.1 IL-5 is elevated in the respiratory tract in eosinophilic lung diseases including eosinophilic pneumonias. In human diseases, the importance of IL-5 is highlighted by monoclonal antibody therapies directed against IL-5 and the IL-5 receptor, which have been highly effective in the treatment of pulmonary eosinophilic disorders including asthma and eosinophilic granulomatosis with polyangiitis.

Activated circulating eosinophils bind to inflamed vascular endothelium and migrate into the tissue in response to chemotactic factors including the CCR3 ligands CCL11, CCL24, and CCL26 (eotaxins 1–3), and lipid mediators such as LTB4 and IL-5.3 High levels of eosinophil chemokines in addition to IL-5 have been demonstrated in the lung and circulation in pulmonary eosinophilic lung diseases.1,4 Elevation in eosinophil cytokines and chemokines is a common pathway by which pulmonary eosinophilia occurs and, in general, does not differentiate among pulmonary eosinophilic disorders. In each of the pulmonary eosinophilic diseases we review here, the triggers that lead to eosinophilia and eosinophil localization in the lung may be different, but there are shared pathways by which eosinophils develop, migrate, and are activated in the lung to cause damage.

The association between pulmonary infiltrates and eosinophilia was first identified by Loeffler in 1932. It is now recognized that the eosinophilic pneumonias are a heterogeneous group of disorders characterized by varying degrees of pulmonary parenchymal and/or blood eosinophilia. The precise role that eosinophils play in the pathogenesis of the different eosinophilic disorders is not clear. Normally, <2% of the leukocytes in the bronchoalveolar lavage (BAL) are eosinophils. The presence of increased BAL and/or tissue eosinophils, and our knowledge of the biology of eosinophils, does, however, suggest that they play ...

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