The Anti-inflammatory Action of Glucocorticoid Hormones

Abstract

Inflammation and immune response are elaborate reactions of mammalian organisms to environmental attacks. As in any stimulated process, the existence of brakes that limit the response, is decisive for survival of the organism. Imagine a bacterial infection: the uncontrolled response, in form of cytokine release by macrophages, e.g. tumour necrosis factor (TNF)-α, would lead to septic shock and death. Excessive TNF-α levels must therefore be avoided by the induction of a brake mechanism. In the chain of reactions between contact with an agent [e.g. lipopolysaccharide (LPS)] and the expression of a program of genes (e.g. TNF-α) numerous inhibitory steps are therefore built in. A particularly important regulatory loop involves the release of glucocorticoids (GCs) which cause downmodulation of proinflammatory transcription factors. This downmodulation is transcriptional, is a function of the glucocorticoid receptor and it is not absolute. In the immune system, partial reduction of signalling or of cytokine synthesis suffices to reach levels below threshold (see, e.g. Viola and Lanzavecchia 1996).