Hypereosinophilia-associated Diseases and the Therapeutic Agents in Development

Il Yup Chung

doi:10.7599/hmr.2013.33.1.65

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Chung: Hypereosinophilia-associated Diseases and the Therapeutic Agents in Development

Review Article

Hanyang Medical Reviews

Hanyang Medical Reviews 2013; 33(1): 65-74.

Published online: 27 February 2013

DOI: https://doi.org/10.7599/hmr.2013.33.1.65

Hypereosinophilia-associated Diseases and the Therapeutic Agents in Development

Il Yup Chung

Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Korea.

Correspondence to: Il Yup Chung. Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Asan 426-791, Korea. Tel: +82-31-400-5514, Fax: +82-31-419-1760, iychu@hanyang.ac.kr

Received 13 November 2012 Revised 4 January 2013 Accepted 11 January 2013

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Asthma, Eosinophils, Interleukin-5, Hypereosinophilic Syndrome

Figures and Tables

Fig. 1

Purified neutrophils and eosinophils from human peripheral blood. After RBC had been precipitated in 6% dextran-dextrose in 0.1 M EDTA (pH 7.4), the leukocyte-rich cell suspension was layered on a Percoll solution (1.070 g/mL) and centrifuged at 3,500×rpm for 30 min at 4℃. The enriched polymorphonuclear fraction were incubated with anti-CD16 monoclonal antibody-conjugated microbeads (Miltenyi Biotec), and neurophils (A) and eosinophils (B) were isolated through positively and negative selection, respectively, using a MACS (BD PharMingen).

Table 1

Anti-eosinophil agents under clinical trials

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