Mechanisms of glucocorticoid action and insensitivity in airways disease

C Boardman; L Chachi; A Gavrila; C R Keenan; M M Perry; Y C Xia; H Meurs; P Sharma

doi:10.1016/j.pupt.2014.08.008

Mechanisms of glucocorticoid action and insensitivity in airways disease

Pulm Pharmacol Ther. 2014 Dec;29(2):129-43. doi: 10.1016/j.pupt.2014.08.008. Epub 2014 Sep 9.

Authors

C Boardman¹, L Chachi², A Gavrila², C R Keenan³, M M Perry¹, Y C Xia³, H Meurs⁴, P Sharma⁵

Affiliations

¹ Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom.
² Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
³ Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
⁴ Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.
⁵ Department of Physiology and Pharmacology, Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 4C46 HRIC, 3280 Hospital Dr NW, Calgary, AB, Canada T2N 4N1. Electronic address: pawan.sharma@jefferson.edu.

PMID: 25218650
DOI: 10.1016/j.pupt.2014.08.008

Abstract

Glucocorticoids are the mainstay for the treatment of chronic inflammatory diseases including asthma and chronic obstructive pulmonary disease (COPD). However, it has been recognized that glucocorticoids do not work well in certain patient populations suggesting reduced sensitivity. The ultimate biologic responses to glucocorticoids are determined by not only the concentration of glucocorticoids but also the differences between individuals in glucocorticoid sensitivity, which is influenced by multiple factors. Studies are emerging to understand these mechanisms in detail, which would help in increasing glucocorticoid sensitivity in patients with chronic airways disease. This review aims to highlight both classical and emerging concepts of the anti-inflammatory mechanisms of glucocorticoids and also review some novel strategies to overcome steroid insensitivity in airways disease.

Keywords: Asthma; Chronic airway diseases; Combination therapy; Glucocorticoid; Inflammation; Steroid resistance.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Anti-Inflammatory Agents / therapeutic use
Asthma / drug therapy
Glucocorticoids / therapeutic use*
Humans
Pulmonary Disease, Chronic Obstructive / drug therapy
Receptors, Glucocorticoid / drug effects
Respiratory Tract Diseases / drug therapy*
Signal Transduction / drug effects
Treatment Outcome

Substances

Anti-Inflammatory Agents
Glucocorticoids
Receptors, Glucocorticoid