Yang, N, Ray, DW and Matthews, LC (2012) Current concepts in glucocorticoid resistance. Steroids, 77 (11). pp. 1041-1049. ISSN 0039-128X
Abstract
Glucocorticoids (GCs) are the most potent anti-inflammatory agents known. A major factor limiting their clinical use is the wide variation in responsiveness to therapy. The high doses of GC required for less responsive patients means a high risk of developing very serious side effects. Variation in sensitivity between individuals can be due to a number of factors. Congenital, generalized GC resistance is very rare, and is due to mutations in the glucocorticoid receptor (GR) gene, the receptor that mediates the cellular effects of GC. A more common problem is acquired GC resistance. This localized, disease-associated GC resistance is a serious therapeutic concern and limits therapeutic response in patients with chronic inflammatory disease. It is now believed that localized resistance can be attributed to changes in the cellular microenvironment, as a consequence of chronic inflammation. Multiple factors have been identified, including alterations in both GR-dependent and -independent signaling downstream of cytokine action, oxidative stress, hypoxia and serum derived factors. The underlying mechanisms are now being elucidated, and are discussed here. Attempts to augment tissue GC sensitivity are predicted to permit safe and effective use of low-dose GC therapy in inflammatory disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Glucocorticoid; Glucocorticoid receptor; Glucocorticoid resistance; Inflammation |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Aug 2016 15:45 |
Last Modified: | 03 Nov 2016 04:09 |
Published Version: | http://dx.doi.org/10.1016/j.steroids.2012.05.007 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.steroids.2012.05.007 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:99711 |