The 11beta-hydroxysteroid dehydrogenase enzymes--arbiters of the effects of glucocorticoids in synovium and bone.

Ever since the first use of cortisone, glucocorticoids have had a controversial role in the treatment of RA. There has been equally controversial research into the possible involvement of endogenous glucocorticoids, and their secretion via the hypothalamic-pituitary-adrenal (HPA) axis, in the development and persistence of inflammatory arthritis. Recently, our understanding of how glucocorticoids act has expanded substantially with the characterization of glucocorticoid-metabolizing enzymes that regulate glucocorticoid action at tissue level. These enzymes, the 11β-hydroxysteroid dehydrogenases, interconvert biologically inactive glucocorticoids such as cortisone and prednisone with their active counterparts, cortisol (hydrocortisone) and prednisolone. Without these enzymes, cortisone and prednisone would be therapeutically useless. Furthermore, in normal individuals, the activities of these enzymes influence the function of other components of the HPA axis. These enzymes are expressed in human synovial tissue and bone and have been implicated in the control of synovial inflammation, the development of periarticular bone loss and the sensitivity of bone to therapeutic glucocorticoids. This article reviews recent findings in this area that highlight the role of these enzymes in rheumatic diseases.