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 language | English |
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Pages (from-to) | 672-7 |
Number of pages | 6 |
Journal | Endocrinology |
Volume | 134 |
Issue number | 2 |
DOIs | |
Publication status | Published - 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