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Differential Regulation of Interleukin-10 (IL-10) and IL-12 by Glucocorticoids In Vitro

Jeroen Visser, Anette van Boxel-Dezaire, Dion Methorst, Tibor Brunt, E. Ronald de Kloet, and Lex Nagelkerken

From the Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden; and the Division of Medical Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands.

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.

Blood, Vol. 91 No. 11 (June 1), 1998: pp. 4255-4264
© 1998 by The American Society of Hematology.


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