Glucocorticoids suppress interleukin-1 receptor antagonist synthesis following induction by endotoxin

E Arzt, J Sauer, T Pollmächer, M Labeur, F Holsboer, J M Reul, G K Stalla

Research output: Contribution to journalArticle (Academic Journal)peer-review

77 Citations (Scopus)

Abstract

Glucocorticoids, as part of their physiological role in the control of inflammatory and immune processes, suppress the expression of IL-1 and other cytokines. We have found a dose-dependent inhibition by dexamethasone (10 nM to 10 microM) of mRNA levels of the recently cloned IL-1 receptor antagonist (IL-1ra) in endotoxin-stimulated human monocytes. At the same concentrations, both dexamethasone and cortisol inhibited the secretion of IL-1ra. These inhibitory effects were reversed by blocking glucocorticoid receptors with the specific antagonist RU 38486, but not by adding exogenous IL-1, even up to 100 ng/ml, to the monocytes. A similar inhibition of IL-1ra mRNA and protein secretion was found in monocytes obtained after dexamethasone administration in vivo. In addition, we observed parallel increases in glucocorticoid and IL-1ra levels following endotoxin administration to normal volunteers. Our results show that glucocorticoids shut down not only IL-1 but also IL-1ra expression, ruling out induction of IL-1ra as part of the glucocorticoid antiinflammatory mechanism. The control of the delicate immunoregulatory balance of the IL-1/IL-1ra system during endotoxemia underscores the physiological importance of glucocorticoids in the final control of immune responses.

Original languageEnglish
Pages (from-to)672-7
Number of pages6
JournalEndocrinology
Volume134
Issue number2
DOIs
Publication statusPublished - Feb 1994

Keywords

  • Adult
  • Blotting, Northern
  • Cells, Cultured
  • Dexamethasone
  • Humans
  • Hydrocortisone
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Kinetics
  • Lipopolysaccharides
  • Male
  • Middle Aged
  • Mifepristone
  • Monocytes
  • RNA, Messenger
  • Sialoglycoproteins

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