The Role of GILZ in Anti-Inflammatory and Immunosuppressive Actions of Glucocorticoids

Chronic inflammatory diseases place a social and financial burden on society. Glucocorticoids, a class of steroid hormones existing in almost every vertebrate, have been exploited for more than 60 years as a therapeutic option for the inflammatory diseases. For example, the therapeutic effects of synthetic glucocorticoids, first observed in rheumatoid arthritis (RA), led to the awarding of a Nobel prize in 1950 (Slocumb et al., 1950). Based on their rapid, profound and wide-ranging effects, glucocorticoids are a mainstay of treatment for virtually all inflammatory diseases besides RA, and now are among the most frequently prescribed of all medications (Hillier, 2007). Indeed, a community practice survey in 2000 indicated that up to 1% of the entire adult population is taking systemic glucocorticoids at any given time (van Staa et al., 2000). Glucocorticoids have widespread systemic effects, particularly on the inflammation and immune response (Barnes, 2006; Chrousos, 1995). However, glucocorticoids are associated with dose dependent side effects, including diabetes mellitus, osteoporosis, weight gain, and hypertension (Huscher et al., 2009), as well as increased risk of cardiovascular events (Davis et al., 2007). Much effort has been expended identifying glucocorticoid anti-inflammatory mechanisms of action (Barnes, 2006; Scha ̈cke et al., 2002). Understanding of the mechanism of action of glucocorticoids is essential in order to devise better ways to treat inflammatory disease, ideally retaining the beneficial effects of glucocorticoids but not their adverse effects.