Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes
Article first published online: 9 MAR 2004
Clinical & Experimental Allergy
Volume 34, Issue 3, pages 406–412, March 2004
How to Cite
Mozo, L., Suárez, A. and Gutiérrez, C. (2004), Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes. Clinical & Experimental Allergy, 34: 406–412. doi: 10.1111/j.1365-2222.2004.01824.x
- Issue published online: 9 MAR 2004
- Article first published online: 9 MAR 2004
- Submitted 1 April 2003; revised 21 July 2003; accepted 18 August 2003
- glucocorticoid receptor;
Background IL-10 plays an immunosuppressive role in inflammatory responses. Increased plasma levels of IL-10 have been detected in patients under glucocorticoid (GC) therapy, indicating that steroids may exert their suppressive effect, in part, by increasing IL-10 production.
Objectives The aim was to define possible mechanisms by which steroids up-regulate IL-10 production. To this end, we have analysed ex vivo the effect of GCs on the constitutive production of IL-10 by lymphocytes and cells of myeloid origin.
Methods Monocytes and T cells were isolated by a Percoll gradient and B cells were purified by rosetting. Protein and mRNA IL-10 levels were determined by ELISA and by Northern blot, respectively.
Results Monocytes, but not T or B cells, up-regulated the constitutive production of IL-10 following pre-treatment for at least 12 h with physiological doses of dexamethasone (Dex). Up-regulation of IL-10 occurred at both protein and mRNA levels, probably indicating that the effect of Dex was by incrementing gene transcription. Other steroids had similar outcomes, their effects being dose-related, proportional to the steroid potency and totally reversed by the steroid antagonist RU486. Thus, transcript levels of IL-10 were up-regulated by GCs probably through binding of the GC receptor to its specific glucocorticoid response element sequence in the IL-10 promoter. In contrast to monocytes, differentiated immature macrophages and dendritic cells did not vary their constitutive IL-10 production after pre-treatment with Dex.
Conclusion Our results support the fact that steroids up-regulate constitutive IL-10 production by selectively triggering activation signals on monocytes.