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Keywords:

  • dexamethasone;
  • glucocorticoids;
  • glucocorticoid receptor;
  • GRE;
  • IL-10;
  • monocytes;
  • pre-treatment;
  • RU486

Summary

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.