Glucocorticoid Mechanisms in Chronic Rhinosinusitis and Nasal Polyposis

Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a persistent inflammatory disorder of the nasal mucosa and paranasal sinuses, often typified by type 2 immune polarisation, eosinophilic infiltration and remodelling of the tissue architecture. Glucocorticoids, whether administered intranasally or systemically, remain the cornerstone of medical management, acting through the glucocorticoid receptor (GR) to modulate gene transcription, repress pro-inflammatory transcription factors (such as NF-κB and AP-1) and enhance anti-inflammatory mediators. Their effects encompass both genomic actions—mediated by GR dimerisation, binding to glucocorticoid response elements and recruitment of histone deacetylases—and rapid non-genomic pathways that influence cellular signalling cascades. Despite their efficacy, a proportion of patients exhibit corticosteroid resistance, linked to altered GR isoform expression, post-receptor signalling defects, epigenetic modifications and local changes in inflammatory mediator networks. Advances in targeted delivery systems and selective GR modulators seek to optimise therapeutic benefit while reducing systemic side-effects. A deeper understanding of glucocorticoid mechanisms is critical for refining treatment algorithms, improving patient outcomes and reducing the global burden of disease.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Glucocorticoid Mechanisms in Chronic Rhinosinusitis and Nasal Polyposis publication trend

The graph below shows the total number of articles in glucocorticoid mechanisms in chronic rhinosinusitis and nasal polyposis across all publications each year (not limited to Nature Index journals).

Technical terms

Glucocorticoid receptor (GR): A cytoplasmic receptor that, upon ligand binding, translocates to the nucleus to regulate gene transcription through glucocorticoid response elements or interaction with other transcription factors.

Type 2 inflammation: An immune response driven by interleukins 4, 5 and 13, associated with eosinophil recruitment, IgE production and mucosal barrier dysfunction in CRSwNP.

Corticosteroid resistance: A clinical state in which inflammatory lesions fail to respond adequately to glucocorticoid therapy, often due to alterations in receptor expression, signalling pathways or chromatin accessibility.

Histone deacetylase 2 (HDAC2): An enzyme that removes acetyl groups from histones, facilitating chromatin condensation and repression of pro-inflammatory gene transcription; its activity is essential for full glucocorticoid efficacy.

Glucocorticoid response element (GRE): A specific DNA sequence within gene promoters to which the GR homodimer binds, modulating expression of target genes involved in immune regulation.

References

1. Expression of glucocorticoid receptor mRNAs in glucocorticoid-resistant nasal polyps. Experimental & Molecular Medicine (2006).
2. Research progress of glucocorticoid resistance in chronic rhinosinusitis with nasal polyps: A review. Medicine (2023).