Glucocorticoid regulation of inflammation: The plot thickens

While glucocorticoids are widely used in the suppression of immune-inflamma tory diseases, much remains unknown about the contribution of endogenous ad renal glucocorticoids to inflammatory regulation. It is now well understood that glucocorticoids are increased by inflammatory stress and provide for responsive limitation of inflammation. It is self-evident that the immune r esponse in healthy animals takes place in a milieu characterised by backgro und levels of glucocorticoids. It is less well appreciated, however, that b asal levels of glucocorticoids may in fact be a requirement for a normal im mune response. In fact, extensive data exist supporting the hypothesis that glucocorticoids interact with the immune-inflammatory system in a biphasic , concentration dependent fashion. No mechanistic explanation for this appa rent paradox has previously existed. Recently, the cytokine macrophage migr ation inhibitory factor (MIF), while possessing pleiotropic pro-inflammator y properties, has been demonstrated to be glucocorticoid-inducible. This ob servation;has the potential to explain key aspects of the biphasic regulati on of inflammatory response by endogenous glucocorticoids.