Anti-inflammatory functions of glucocorticoid-induced genes

There is a broad consensus that glucocorticoids (GCs) exert anti-inflammatory effects largely by inhibiting the function of nuclear factor kappa B (NF kappa B) and consequently the transcription of pro-inflammatory genes. In contrast, side effects are thought to be largely dependent on GC-induced gene expression. Biochemical and genetic evidence suggests that the positive and negative effects of GCs on transcription can be uncoupled from one another. Hence, novel GC-related drugs that mediate inhibition of NF kappa B but do not activate gene expression are predicted to retain therapeutic effects but cause fewer or less severe side effects. Here, we critically re-examine the evidence in favor of the consensus, binary model of GC action and discuss conflicting evidence, which suggests that anti-inflammatory actions of GCs depend on the induction of anti-inflammatory mediators. We propose an alternative model, in which GCs exert anti-inflammatory effects at both transcriptional and post-transcriptional levels, both by activating and inhibiting expression of tat-get genes. The implications of such a model in the search for safer anti-inflammatory drugs are discussed. (c) 2007 Elsevier Ireland Ltd. All rights reserved.