Dexamethasone suppressed gene expression and production of interleukin-10 by human peripheral blood mononuclear cells and monocytes.
Interleukin-10 (IL-10) is known to inhibit T cell-mediated responses. IL-10 has also been shown to play an important pathogenetic role in allergic diseases. Glucocorticoid is known to inhibit the production and gene expression of many cytokines which induce inflammatory reactions. We examined the effect of dexamethasone on the gene expression and production of IL-10 by human peripheral blood mononuclear cells (PBMCs) and monocytes. PBMCs and monocytes from 5 healthy volunteers were incubated with or without dexamethasone for 1 h, then stimulated with 5 micrograms/ml lipopolysaccharide (LPS). Gene expression and production of IL-10 by human PBMCs were detected without stimulation and increased by LPS stimulation. Dexamethasone suppressed the gene expression and production of IL-10 by LPS-stimulated PBMCs in a dose-dependent manner by 41.6 and 61.1% at 10(-6) M, respectively. Also in monocytes, the gene expression and production of IL-10 were detected without stimulation, increased by LPS stimulation, and significantly suppressed by dexamethasone by 53.1 and 61.2% at 10(-6) M, respectively. This suppressive effect on IL-10 gene expression was not so potent compared with its effect on cytokines such as IL-5. The suppression of IL-10 production by glucocorticoid is suggested to be one of the important mechanisms by which glucocorticoids suppress allergic inflammation in the treatment of allergic diseases.
Fushimi
T
T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Okayama
H
H
Seki
T
T
Shimura
S
S
Shirato
K
K
D015152:Blotting, Northern; D002469:Cell Separation; D002478:Cells, Cultured; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis
D017931:DNA Primers; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D012313:RNA; D003907:Dexamethasone