Eosinophil Apoptosis as a Therapeutic Target in Allergic Asthma

Basic and Clinical Pharmacology and Toxicology - Tập 114 Số 1 - Trang 109-117 - 2014
Pinja Ilmarinen1, Hannu Kankaanranta2,1
1The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland
2Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland and University of Tampere, Tampere, Finland

Tóm tắt

AbstractAsthma is a chronic inflammatory disease of the airways manifesting in many different phenotypes. Allergic asthma, comprising approximately half of patients with asthma, is characterized by the accumulation of eosinophils into the lungs. Eosinophils release factors that damage the surrounding cells and participate in the maintenance and exacerbation of inflammation. In the absence of any inflammatory survival‐prolonging factors, eosinophils die by apoptosis in few days but in inflamed airways, eosinophil survival is thought to be prolonged due to the surrounding pro‐inflammatory factors such as IL‐5, IL‐3 and GM‐CSF. Resolution of eosinophilic inflammation is an important goal in the treatment of allergic asthma. Apoptosis is a physiological and non‐inflammatory way to eliminate these harmful cells, and development of drugs targeting eosinophil apoptosis is one possible strategy for the therapy of allergic asthma. Importance of this strategy is supported by the fact that promotion of eosinophil apoptosis is a property of many anti‐asthmatic agents such as glucocorticoids, the current main anti‐inflammatory therapy of asthma, theophylline and leukotriene modifiers. β2 agonists have been shown to modulate eosinophil longevity by increasing survival. Also, anti‐IL‐5 antibody mesolizumab has shown efficacy in reducing asthma exacerbations in patients with severe eosinophilic asthma. Many potential future anti‐asthmatic agents, such as Siglec‐8 activating antibody and novel humanized anti‐IL‐5 antibody MEDI‐563, have the property of inducing eosinophil apoptosis. This MiniReview aims to present eosinophil apoptosis as a therapeutic target in the treatment of allergic asthma. We summarize the effects and mechanisms of current and potential future anti‐asthmatic drugs on eosinophil apoptosis and additionally, discuss the potential factors that promote eosinophil longevity in the lungs.

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Basic and Clinical Pharmacology and Toxicology

Tập 114 Số 1

109-117

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