GLUCOCORTICOID MODULATION OF HUMAN MONOCYTE MACROPHAGE FUNCTION - CONTROL OF TNF-ALPHA SECRETION/

Glucocorticoids suppress many functions in activated monocyte/macropha ges, including the release of TNF-alpha. This is likely to contribute to the efficacy of glucocorticoids in some inflammatory diseases, such as rheumatoid arthritis, where TNF-alpha contributes to pathogenesis. Glucocorticoids suppress the activity of reporters which include TNF- alpha promoter regions and modify the activity of NF-kappa B family tr anscription factors in activated human monocytic cell lines, suggestin g effects of glucocorticoids on TNF-alpha gene transcription. In addit ion, glucocorticoids have been reported to antagonise the enhanced tra nslational efficiency of TNF-alpha mRNA which occurs at least after st imulation of murine monocytic cells. It is likely, therefore, that glu cocorticoids act at several points in stimulated monocyte/macrophages to reduce TNF-alpha secretion. Understanding glucocorticoid control of TNF-alpha secretion may explain some of the variability in response t o GC in inflammatory diseases and may reveal means of inducing glucoco rticoid-like anti-inflammatory effects in monocyte/macrophages without exposing other tissues to the adverse effects of glucocorticoids.