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'.

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.