Glucocorticoids in the treatment of rheumatic diseases: An update on the mechanisms of action

Abstract

Six years after we published our first article on the mechanisms of action of glucocorticoids (GCs) (1), there is already a need for an update. GCs are superior to many drugs in terms of the number of patients treated, the variety of potential uses, and the experience with treatment in humans. They still represent the most important and most frequently used class of antiinflammatory drugs, and their therapeutic use has risen continuously in recent years (2). About 10 million new prescriptions for oral GCs are written each year in the US alone (2). They are the silent companions of rheumatologists, and it is impossible to imagine therapy— especially oral therapy, but intravenous and intraarticular as well—without them. From community survey data, the frequency of oral GC use has been estimated to be 0.5% of the general population and 1.75% of women over the age of 55 years (3,4). Between 56% and 68% of patients with rheumatoid arthritis are treated more or less continuously with GCs (5–8). GCs are relatively inexpensive drugs, but it is the sheer volume used that is significant overall; the total market size is believed to be about 10 billion US dollars per year (2). Our understanding of the actions of GCs has also greatly increased in the last few years. In this review, we report on recent insights relating to 1) signaling, transcription processes, and gene expression as induced, inhibited, and/or modified by the interaction of GCs with their cytosolic receptors, 2) relationships between dosages and plasma levels, 3) membrane-bound GC receptors (GCRs), and 4) new (glucocorticoid) drugs on the horizon. These data support the modular concept we proposed in 1998 (1), and so this update follows the same structure.