Hypereosinophilia-associated Diseases and the Therapeutic Agents in Development

Abstract

Eosinophil is one of the most enigmatic leukocytes that plays pleiotropic roles in initiation and propagation of inflammatory conditions, modulation of innate and adaptive immune responses, homeostasis, and remodeling and repair of diverse tissues in health and disease. Eosinophils arise from CD34+ hematopoietic cells in the bone marrow under the influence of transcription factors (C/EBPα and GATA-1) and hematopoietic cytokines (IL-5, IL-3, and GM-CSF). The unusually high numbers of eosinophils in blood and/or tissues, so-called hypereosinophilia, are often critically involved in pathophysiology of a wide variety of inflammatory diseases in many organs, including many allergic diseases (asthma, rhinitis, conjunctivitis, atopic dermatitis), gastrointestinal diseases (eosinophilic eosophagitis, ulcerative colitis, Crohn's disease, Duchenne's muscular dystrophy, idiopathic myositis), cancers (pancreas, bladder, liver, kidney, breast, melanoma, colon, glioblastoma, gastric, uterine, oral/nasal, lung), infectious diseases (helminth, bacteria, virus, fungi), transplantation rejection (lung, cardiac, corneal, skin, liver, and renal), reproduction, and autoimmune diseases. A dozen of therapeutic agents, notably including humanized anti-IL-5 monoclonal antibodies, that directly and indirectly target eosinophils have been developed and are studied extensively under clinical and preclinical trials. Some agents have been shown to have promising perspectives to hypereosinophilic diseases, especially against asthma exacerbations and hypereosinophilic syndromes. Further studies are required for discovery of the specific mechanisms of actions of the different eosinophil-targeted therapies, dosing strategies and treatment options with identification of biomarkers that can monitor and predict the responses.