Optimized glucocorticoid therapy: teaching old drugs new tricks.

Glucocorticoids (GCs) are commonly used in the treatment of a wide range of rheumatic and other inflammatory diseases. They exert their potent anti-inflammatory and immunosuppressive effects primarily via so called genomic mechanisms, mediated by the cytosolic glucocorticoid receptor (cGR). This mechanism of GC action can be divided into the transactivation and the transrepression processes. However, also rapid effects of GCs exist which are mediated by specific and unspecific non-genomic mechanisms. A clinical relevance of this mode of GC action is assumed for effects mediated by membrane-bound glucocorticoid receptors, but detailed knowledge on the underlying mechanisms is still missing. Great efforts have been made in the past to diminish GC-induced adverse effects, thus improving the benefit/risk ratio of the drugs. Besides approaches to improve the treatment with conventional glucocorticoids currently available to clinicians, new innovative GCs or GC receptor ligands are also being developed.