Abstract.
Glucocorticoid drugs affect virtually every cell type involved in inflammatory response, to some degree. Macrophage/monocytes (Mφ) are particularly sensitive, and glucocorticoids suppress release of most known Mφ inflammatory mediators, including TNF-α. In the case of TNF-α, several levels of regulation are already characterised and ongoing research hints at further glucocorticoid targets. The relative importance of transcriptional and post-transcriptional regulation is lineage-dependent and may also change during the course of Mφ differentiation. In human monocytic cell lines, glucocorticoids primarily suppress transcriptional activation through adjacent promoter binding sites for NF-κB transcription factor complexes and for complexes of c-Jun with activating transcription factor-2 (ATF-2). The goal of glucocorticoid research in inflammation is to develop drugs with the anti-inflammatory potential of glucocorticoids, but without the systemic toxicity. Each of the multiple targets for glucocorticoid action presents an opportunity for anti-inflammatory drug development. However, none of the known targets is unique to Mφ, and no single pathway is preeminent in all situations. Research is now directed at characterising targets and regulating them without systemic activation of the glucocorticoid receptor.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received 11 August 2000; returned for revision 27 February 2001; accepted by R. Day 1 March 2001
Rights and permissions
About this article
Cite this article
Joyce, D., Gimblett, G. & Steer, J. Targets of glucocorticoid action on TNF-α release by macrophages. Inflamm. res. 50, 337–340 (2001). https://doi.org/10.1007/PL00012387
Issue Date:
DOI: https://doi.org/10.1007/PL00012387