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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 237))

Abstract

The most effective anti-inflammatory drugs used to treat patients with airways disease are topical glucocorticosteroids (GCs). These act on virtually all cells within the airway to suppress airway inflammation or prevent the recruitment of inflammatory cells into the airway. They also have profound effects on airway structural cells to reverse the effects of disease on their function. Glucorticosteroids act via specific receptors—the glucocorticosteroid receptor (GR)—which are a member of the nuclear receptor family. As such, many of the important actions of GCs are to modulate gene transcription through a number of distinct and complementary mechanisms. Targets genes include most inflammatory mediators such as chemokines, cytokines, growth factors and their receptors. GCs delivered by the inhaled route are very effective for most patients and have few systemic side effects. However, in some patients, even high doses of topical or even systemic GCs fail to control their disease. A number of mechanisms relating to inflammation have been reported to be responsible for the failure of these patients to respond correctly to GCs and these provide insight into GC actions within the airways. In these patients, the side-effect profile of GCs prevent continued use of high doses and new drugs are needed for these patients. Targeting the defective pathways associated with GC function in these patients may also reactivate GC responsiveness.

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Acknowledgements

Research in the author’s laboratories is supported by the EU (IMI), MRC (UK), Wellcome Trust, BHF, Dunhill Medical Trust and by Asthma UK. The authors have no conflicts of interest. IMA is a principal investigator in the MRC/Asthma UK Centre for Asthma and Allergic Mechanisms and is supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.

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Adcock, I.M., Mumby, S. (2016). Glucocorticoids. In: Page, C., Barnes, P. (eds) Pharmacology and Therapeutics of Asthma and COPD. Handbook of Experimental Pharmacology, vol 237. Springer, Cham. https://doi.org/10.1007/164_2016_98

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