Targeting eosinophils in asthma: current and future state of cytokine- and chemokine-directed monoclonal therapy

Walsh, Garry Michael

doi:10.1586/eci.10.58

Cited by 16 publications

(12 citation statements)

References 23 publications

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“…The recruit of eosinophils into the epithelium and eosinophilic inflammation is involved in the pathogenesis of asthma. The proinflammatory mediators derived by eosinophil are major contributors to inflammation in asthma, including airway epithelial cell damage and desquamation, airway dysfunction of cholinergic nerve receptors, AHR, mucus hypersecretion, and airway remodeling, characterized by fibrosis and collagen deposition (Kay, 2005; Watt et al, 2005; Kanda et al, 2009; Walsh, 2010). Eosinophils are likely to contribute to airway remodeling with release of eosinophil-derived mediators such as TGF-β, secretion of cationic proteins, and cytokines, as well as having interactions with mast cell and epithelial cells.…”

Section: Mast Cells and Eosinophilsmentioning

confidence: 99%

Pathology of asthma

Kudo¹,

Ishigatsubo²,

Aoki³

2013

Front. Microbiol.

299

213

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Asthma is a serious health and socioeconomic issue all over the world, affecting more than 300 million individuals. The disease is considered as an inflammatory disease in the airway, leading to airway hyperresponsiveness, obstruction, mucus hyper-production and airway wall remodeling. The presence of airway inflammation in asthmatic patients has been found in the nineteenth century. As the information in patients with asthma increase, paradigm change in immunology and molecular biology have resulted in an extensive evaluation of inflammatory cells and mediators involved in the pathophysiology of asthma. Moreover, it is recognized that airway remodeling into detail, characterized by thickening of the airway wall, can be profound consequences on the mechanics of airway narrowing and contribute to the chronic progression of the disease. Epithelial to mesenchymal transition plays an important role in airway remodeling. These epithelial and mesenchymal cells cause persistence of the inflammatory infiltration and induce histological changes in the airway wall, increasing thickness of the basement membrane, collagen deposition and smooth muscle hypertrophy and hyperplasia. Resulting of airway inflammation, airway remodeling leads to the airway wall thickening and induces increased airway smooth muscle mass, which generate asthmatic symptoms. Asthma is classically recognized as the typical Th2 disease, with increased IgE levels and eosinophilic inflammation in the airway. Emerging Th2 cytokines modulates the airway inflammation, which induces airway remodeling. Biological agents, which have specific molecular targets for these Th2 cytokines, are available and clinical trials for asthma are ongoing. However, the relatively simple paradigm has been doubted because of the realization that strategies designed to suppress Th2 function are not effective enough for all patients in the clinical trials. In the future, it is required to understand more details for phenotypes of asthma.

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Section: Mast Cells and Eosinophilsmentioning

confidence: 99%

Pathology of asthma

Kudo¹,

Ishigatsubo²,

Aoki³

2013

Front. Microbiol.

299

213

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“…And airway hyperresponsiveness is a well-established consequence of eosinophil infiltration (Kay, 2005; Watt et al, 2005; Kanda et al, 2009; Kim and Lee, 2009; Walsh, 2010). There is evidence that eosinophils are involved in the bronchial hyperresponsiveness mediated by T-cell (Ohtomo et al, 2010).…”

Section: Airway Hyperresponsivenessmentioning

confidence: 99%

“…Allergic asthma is associated with eosinophilic inflammation in the airways (Lu et al, 2010). The proinflammatory mediators derived by eosinophil are major contributors to inflammation in asthma, including airway epithelial cell damage and loss, airway dysfunction of cholinergic nerve receptors, airway hyperresponsiveness, mucus hypersecretion, and airway remodeling, characterized by fibrosis and collagen deposition (Kay, 2005; Watt et al, 2005; Kanda et al, 2009; Walsh, 2010). Currently, the term “eosinophilic asthma” has been used to characterize an asthma phenotype with prevalence of eosinophils in the bronchial airways, and this phenotype can be identified by peripheral eosinophil count (Liang et al, 2012; Molfino, 2012; Spector and Tan, 2012).…”

Section: Introductionmentioning

confidence: 99%

Eosinophilic Inflammation in Allergic Asthma

et al. 2013

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Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma.

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“…The cytokine panel included IL-5, IL-7 and IL-13, inflammatory cytokines implicated in eosinophilic asthma triggered by the TH2 pathway, IL-8, crucial in neutrophil recruitment [14][15][16], and Tumor Necrosis Factor-alpha (TNF-α) that has a central role in systemic inflammation [10]. Additionally, this panel included two cytokines that are less often investigated in asthma [12]: Interleukin (IL)-1 receptor antagonist (IL-1Ra), an antagonist of IL-1 with antiinflammatory activity [17], and IL-10 able to inhibit pro-inflammatory cytokine synthesis [18,19].…”

Section: Introductionmentioning

confidence: 99%