Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes.
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.


OBJECTIVE
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.


CONCLUSIONS
Our results support the fact that steroids up-regulate constitutive IL-10 production by selectively triggering activation signals on monocytes.
Department of Immunology, Hospital Central de Asturias, Centro Universitario, Oviedo, Spain.
L
L
Mozo
A
A
Suárez
C
C
Gutiérrez
D015152:Blotting, Northern / Q000379:methods; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D015735:Mifepristone / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020298:U937 Cells; D015854:Up-Regulation
D005938:Glucocorticoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D016753:Interleukin-10; D015735:Mifepristone; D003907:Dexamethasone