DIFFERENTIAL REGULATION OF INTERLEUKIN-10 (IL-10) AND IL-12 BY GLUCOCORTICOIDS IN-VITRO

Antigen-presenting cells are thought to modulate the development of Th 1 and Th2 cells by the secretion of interleukin-10 (IL-10) and IL-12, Because glucocorticoids (GC) favor the development of Th2 responses, w e determined whether dexamethasone (DEX) and hydrocortisone (HC) have differential effects on lipopolysaccharide-induced IL-10 and IL-12 pro duction 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 respec tively, whereas IL-10 was relatively insensitive or even stimulated. A ccordingly, the expression of IL-12(p40) and IL-12(p35) mRNA was more sensitive to DEX than IL-10 mRNA. The glucocorticoid receptor (GR) ant agonist RU486 enhanced IL-12 production and largely abrogated the inhi bition of IL-12 by GC, indicating that this suppression was mainly GR- mediated. High concentrations of RU486 were inhibitory for IL-10, sugg esting that GC may exert a positive effect on IL-10. In the presence o f neutralizing anti-IL-10 antibodies, DEX was still capable of IL-12 s uppression whereas RU486 still enhanced IL-12 production, indicating t hat GC do not modulate IL-12 via IL-10 exclusively. Taken together the se results indicate that GC may favor Th2 development by differential regulation of IL-10 and IL-12. (C) 1998 by The American Society of Hem atology.