ArticleAnnals of the rheumatic diseases2021
Local steroid activation is a critical mediator of the anti-inflammatory actions of therapeutic glucocorticoids.
Article in Annals of the rheumatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Meta-analysis of the efficacy and safety of vamorolone in Duchenne muscular dystrophy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis.Frontiers in neurology · 2023Pooled it
- High-salt diet modulates endocrine regulation between cortisol and FGF23.Pflugers Archiv : European journal of physiology · 2026Article
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.Nature immunology · 2026Article
- Pharmacological Interventions in the Management of Sports Injuries: A Review of Clinical Use, Dosage Forms, and Anti-Doping Considerations.Drug design, development and therapy · 2026Review
- The local inactivation of glucocorticoid as regulator for the development of glucocorticoid-induced osteoporosis.PNAS nexus · 2025Article
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.bioRxiv : the preprint server for biology · 2025Article
- Vamorolone: a novel metabolism resistant steroid that suppresses joint destruction in chronic polyarthritis with reduced systemic side effects.Rheumatology (Oxford, England) · 2025Article
- Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space.Advanced healthcare materials · 2025Article
- Impact of initial postweaning feed intake on weanling piglet metabolism, gut health, and immunity.Journal of animal science · 2025Article
- Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity.Nature communications · 2024Article
- Drug-Induced Atypical Lipodystrophy.JCEM case reports · 2024Article
- 11β hydroxysteroid dehydrogenase type 1 transgenic mesenchymal stem cells attenuate inflammation in models of sepsis.Frontiers in bioengineering and biotechnology · 2024Article
- Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?Endocrine reviews · 2023Review
- Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β.Frontiers in immunology · 2023Article
- Impaired alveolar macrophage 11β-hydroxysteroid dehydrogenase type 1 reductase activity contributes to increased pulmonary inflammation and mortality in sepsis-related ARDS.Frontiers in immunology · 2023Article
- Do Corticosteroid Receptor mRNA Levels Predict the Expression of Their Target Genes?Journal of the Endocrine Society · 2022Article
- Impact of Glucocorticoids on Cardiovascular System-The Yin Yang Effect.Journal of personalized medicine · 2022Review
- 11β-Hydroxysteroid Dehydrogenase Type 1 within Osteoclasts Mediates the Bone Protective Properties of Therapeutic Corticosteroids in Chronic Inflammation.International journal of molecular sciences · 2022Article
- Effects ofFrontiers in bioengineering and biotechnology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesThe enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a well-characterised role in the metabolism and activation of endogenous glucocorticoids (GCs). However, despite its potent upregulation at sites of inflammation, its role in peripheral metabolism and action of therapeutic GCs remains poorly understood. We investigated the contribution of 11β-HSD1 to the anti-inflammatory properties of the active GC corticosterone, administered at therapeutic doses in murine models of polyarthritis.
methodsUsing the tumour necrosis factor-tg and K/BxN serum-induced models of polyarthritis, we examined the anti-inflammatory properties of oral administration of corticosterone in animals with global, myeloid and mesenchymal targeted transgenic deletion of 11β-HSD1. Disease activity and joint inflammation were scored daily. Joint destruction and measures of local and systemic inflammation were determined by histology, micro-CT, quantitative RT-PCR, fluorescence activated cell sorting and ELISA.
resultsGlobal deletion of 11β-HSD1 resulted in a profound GC resistance in animals receiving corticosterone, characterised by persistent synovitis, joint destruction and inflammatory leucocyte infiltration. This was partially reproduced with myeloid, but not mesenchymal 11β-HSD1 deletion, where paracrine GC signalling between cell populations was shown to overcome targeted deletion of 11β-HSD1.
conclusionsWe identify an entirely novel component of therapeutic GC action, whereby following their systemic metabolism, they require peripheral reactivation and amplification by 11β-HSD1 at sites of inflammation to deliver their anti-inflammatory therapeutic effects. This study provides a novel mechanistic understanding of the anti-inflammatory properties of therapeutic GCs and their targeting to sites of inflammation in polyarthritis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.