Steroid Resistance in Asthma: Mechanisms and Treatment Options

Overview

Journal Curr Allergy Asthma Rep

Specialties Allergy & Immunology
Pulmonary Medicine

Date 2008 Apr 18

PMID 18417060

Citations 34

Authors

Ian M Adcock

Paul A Ford

Pank Bhavsar

Tehireem Ahmad

Kian Fan Chung

Affiliations

Soon will be listed here.

Abstract

Glucocorticoid insensitivity presents a profound management problem in patients with asthma because conventional therapies are not effective. Glucocorticoids, acting through the glucocorticoid receptor (GR), are able to selectively repress inflammatory gene expression by utilizing several distinct mechanisms targeting nuclear factor-varphiB and activator protein-1 activation complexes and by effects on mitogen-activated protein kinases. Different model systems often activate distinct sets of signaling molecules and different glucocorticoid responsiveness may result from differences in concentrations and timing of steroid treatment of cells, GR expression levels, and the precise inflammatory stimulus used. Thus, abnormal activation of many signaling pathways may affect corticosteroid responsiveness in patients with corticosteroid-resistant asthma. Understanding the molecular mechanisms of GR action and inaction may lead to the development of new anti-inflammatory drugs or enable clinicians to reverse the relative steroid-insensitivity that is characteristic of some patients with severe asthma.

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