title: Glucocorticoids and chronic inflammation.
abstract: Glucocorticoids are steroid hormones that once bound to their receptor interact with the DNA binding domain. Almost 1000-2000 genes are sensitive to their effects, including immune/inflammatory response genes. However, their role in pathophysiology and therapy is still debated. We performed a literature survey using the key words glucocorticoids, inflammation, autoimmune disease, rheumatology and adrenal glands in order to define important targets for this review on glucocorticoids. Considering endogenous/exogenous glucocorticoids in chronic inflammatory diseases brought up five major points for discussion: inadequately low production of endogenous cortisol relative to systemic inflammation (the disproportion principle); changes of the systemic and local cortisol-to-cortisone shuttle (reactivation and degradation of cortisol); inflammation-induced glucocorticoid resistance; highlights of present glucocorticoid therapy; and the role of circadian rhythms in action of cortisol. Much of this information becomes understandable in the context of neurohormonal energy regulation as recently summarized. The optimization of long-term low-dose glucocorticoid therapy in chronic inflammatory diseases arises from the understanding of the above mentioned aspects. Since glucocorticoid resistance is a consequence of inflammation, adequate anti-inflammatory therapy is mandatory.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine, University Hospital Regensburg, Germany rainer.straub@ukr.de.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.affiliation: Research Laboratories and Academic Unit of Clinical Rheumatology, Postgraduate School of Rheumatology, Department of Internal Medicine, University of Genova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D002940:Circadian Rhythm / Q000276:immunology*; D003348:Cortisone / Q000276:immunology*; D005938:Glucocorticoids / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*
chemical_list: D005938:Glucocorticoids; D003348:Cortisone; D006854:Hydrocortisone
keywords: cortisol-to-cortisone shuttle; glucocorticoid resistance; glucocorticoids; relative adrenal insufficiency; role of circadian rhythm; substitution of the adrenal gland