[Glucocorticoids at the threshold of the new millennium: recent findings on the anti-inflammatory and immunomodulator mechanisms of action and future perspectives].

: The aim of this work was to provide an updated review of the mechanisms of action of glucocorticoids. We carried out a MEDLINE search (1970 to present) using "glucocorticoids" as the keyword, both on its own (subheadings: "genetics, immunology, metabolism, physiology, therapeutic use") and combined with "inflammation", "glucocorticoid response element", "gene expression regulation", "NF-kappa B", "transcription factor AP-1", "receptors, glucocorticoid", "chemokines", "cytokines", "cytokine receptors", "resistance", "sensitivity", "annexin-I", "apoptosis", "repressors" and "activators", respectively. Original, partially unpublished data from our research group was also reported. Although we reviewed the sources available, we did not adopt any statistic procedures for data extraction, as the review deals only with basic research. The results of this review indicate that glucocorticoids act through different mechanisms: they can regulate the transcription of a number of genes (genomic mechanisms), interfere with cell activation factors (mechanisms of repression of cell activation factors), and inhibit cell activation via a direct interaction with the cell membrane and/or some of its components (non-genomic mechanisms). There is some evidence that most of the anti-inflammatory effects of glucocorticoids are mediated by repression of transcriptor factors, whereas their metabolic effects appear to be predominantly mediated by genomic mechanisms. This observation has prompted the search for new steroid compounds endowed with more selective anti-inflammatory properties than those currently available. We conclude that better understanding of the mechanisms of action of steroids may result in the development of new molecules with a better risk/benefit ratio.