title: Changing glucocorticoid action: 11β-hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation.
abstract: Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled 'CSR 2013'.
authors: University/BHF Centre for Cardiovascular Sciences, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Electronic address: Karen.Chapman@ed.ac.uk.
authors: Karen E
authors: KE
authors: Chapman
authors: Agnes E
authors: AE
authors: Coutinho
authors: Zhenguang
authors: Z
authors: Zhang
authors: Tiina
authors: T
authors: Kipari
authors: John S
authors: JS
authors: Savill
authors: Jonathan R
authors: JR
authors: Seckl
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000208:Acute Disease; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1
keywords: 11β-HSD; 11β-Hydroxysteroid dehydrogenase; 11β-hydroxysteroid dehydrogenase; Arthritis; C/EBP; CCAAT/enhancer binding protein; EGR-1; Glucocorticoid; H6PD; HPA; IL; Inflammation; LPS; MCP; Macrophage; Mineralocorticoid; NF-κB; TNF-α; VCAM; early growth response-1; hexose-6-phosphate dehydrogenase; hypothalamic–pituitary–adrenal; interleukin; lipopolysaccharide; monocyte chemotactic protein; nuclear factor kappa-light-chain-enhancer of activated B cells; tumour necrosis factor-α; vascular cell adhesion molecule