Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro.
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.
Visser
J
J
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
van Boxel-Dezaire
A
A
Methorst
D
D
Brunt
T
T
de Kloet
E R
ER
Nagelkerken
L
L
D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000502:physiology; D018418:Th2 Cells / Q000166:cytology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D005938:Glucocorticoids; D006727:Hormone Antagonists; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015735:Mifepristone; D003907:Dexamethasone; D006854:Hydrocortisone