Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive asthma.
Am J Respir Crit Care Med
; 190(6): 639-48, 2014 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-25133876
ABSTRACT
RATIONALE Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown. OBJECTIVES:
To determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma.METHODS:
We analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide. MEASUREMENTS AND MAINRESULTS:
Epithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment.CONCLUSIONS:
IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asma
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Corticoesteroides
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Células Th2
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Antiasmáticos
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Interleucina-17
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Células Epiteliales
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2014
Tipo del documento:
Article