Impact of downstream effects of glucocorticoid receptor dysfunction on organ function in critical illness-associated systemic inflammation

Abstract

Abstract Glucocorticoids (GCs) are stress hormones that regulate developmental and physiological processes and are among the most potent anti-inflammatory drugs to suppress chronic and acute inflammation. GCs act through the glucocorticoid receptor (GR), a ubiquitously expressed ligand-activated transcription factor, which translocates into the nucleus and can act via two different modes, as a GR monomer or as a GR dimer. These two modes of action are not clearly differentiated in practice and may lead to completely different therapeutic outcomes. Detailed aspects of GR mechanisms are often not taken into account when GCs are used in different clinical scenarios. Patients, with critical illness-related corticosteroid insufficiency, treated with natural or synthetic GCs are still missing a clearly defined therapeutic strategy. This review discusses the different modes of GR function and its importance on organ function in vivo.

Keywords

• Glucocorticoid receptor
• Dysfunction
• Monomer
• Dimer
• Systemic inflammation
• Mouse models