GLUCOCORTICOIDS INHIBIT THE PRODUCTION OF IL-6 FROM MONOCYTES, ENDOTHELIAL-CELLS AND FIBROBLASTS

We have examined the effect of dexamethasone (DM) and cortisol on the production of interleukin (IL)6 from the murine macrophage cell line RAW 264.9, human monocytes, human endothelial cells and the human fibroblast cell line FS4. In RAW 264.9 cells DM in the concentration range 10−9 M to 10−6 M inhibited the lipopolysaccharide (LPS)‐induced production of IL 6 by 10% to 90%. Cortisol had a similar effect, but was about 25 times less potent than DM. Also, when 10−6 M of DM was added to the cultures after addition of LPS, it completely inhibited the residual 24‐h production of IL 6. Corresponding to the effect on IL 6 production, DM (10−6 M) reduced the mRNA levels for IL 6 in the RAW 264.9 cells. The glucocorticoid analogue RU 486 competes with DM and cortisol for the glucocorticoid receptor and reversed the inhibitory effect of DM, demonstrating that DM exerts its effect via the glucocorticoid receptor. DM also had an inhibitory effect on LPS‐stimulated IL 6 production in freshly isolated human monocytes, and on IL 1‐stimulated IL 6 production in human endothelial cells and FS4 fibroblasts. These results demonstrate that DM via a receptormediated mechanism inhibits IL 6 production at the transcriptional level, and this may contribute to the anti‐inflammatory and immunosuppressive effect of glucocorticoids. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim