Hanyang Med Rev.  2013 Feb;33(1):65-74. 10.7599/hmr.2013.33.1.65.

Hypereosinophilia-associated Diseases and the Therapeutic Agents in Development

• Chung IY

• KMID: 2168223
• DOI: http://doi.org/10.7599/hmr.2013.33.1.65

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/EBPalpha 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.

Keyword

Asthma; Eosinophils; Interleukin-5; Hypereosinophilic Syndrome

MeSH Terms

Antibodies, Monoclonal
Asthma
Autoimmune Diseases
Bacteria
Bone Marrow
Breast
Colitis, Ulcerative
Colon
Communicable Diseases
Conjunctivitis, Allergic
Crohn Disease
Cytokines
Eosinophils
Gastrointestinal Diseases
Glioblastoma
Graft Rejection
Homeostasis
Humans
Hypereosinophilic Syndrome
Interleukin-3
Interleukin-5
Kidney
Leukocytes
Liver
Melanoma
Muscular Dystrophies
Organothiophosphorus Compounds
Reproduction
Rhinitis
Skin
Transcription Factors
Urinary Bladder
Viruses
Biomarkers
Antibodies, Monoclonal
Cytokines
Interleukin-3
Interleukin-5
Organothiophosphorus Compounds
Transcription Factors

Figure

• 

  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).

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