Title
Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro
Author
Visser, J.
van Boxel-Dezaire, A.
Methorst, D.
Brunt, T.
de Kloet, E.R.
Nagelkerken, L.
TNO Preventie en Gezondheid
Publication year
1998
Abstract
Antigen-presenting cells are thought to modulate the development of Th1 and Th2 cells by the secretion of interleukin-10 (IL-10) and IL-12. Because glucocorticoids (GC) favor the development of Th2 responses, we determined whether dexamethasone (DEX) and hydrocortisone (HC) have differential effects on lipopolysaccharide-induced IL-10 and IL-12 production in whole-blood cultures. Significant inhibition of IL-12(p40) and IL-12(p70) was found with 10-8 mol/L and 10-9 mol/L DEX respectively, whereas IL-10 was relatively insensitive or even stimulated. Accordingly, the expression of IL-12(p40) and IL-12(p35) mRNA was more sensitive to DEX than IL-10 mRNA. The glucocorticoid receptor (GR) antagonist RU486 enhanced IL-12 production and largely abrogated the inhibition of IL-12 by GC, indicating that this suppression was mainly GR-mediated. High concentrations of RU486 were inhibitory for IL-10, suggesting that GC may exert a positive effect on IL-10. In the presence of neutralizing anti-IL-10 antibodies, DEX was still capable of IL-12 suppression whereas RU486 still enhanced IL-12 production, indicating that GC do not modulate IL-12 via IL-10 exclusively. Taken together these results indicate that GC may favor Th2 development by differential regulation of IL- 10 and IL-12.
Subject
Health
Antigen-Presenting Cells
Cells, Cultured
Dexamethasone
Female
Glucocorticoids
Hormone Antagonists
Humans
Hydrocortisone
Interleukin-10
Interleukin-12
Lipopolysaccharides
Male
Mifepristone
Receptors, Glucocorticoid
RNA, Messenger
Th1 Cells
Th2 Cells
Tumor Necrosis Factor-alpha
Up-Regulation
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TNO identifier
234483
ISSN
0006-4971
Source
Blood, 91 (11), 4255-4264
Document type
article