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  • 标题:IL-1β Genotype-Related Effect of Prednisolone on IL-1β Production in Human Peripheral Blood Mononuclear Cells under Acute Inflammation
  • 本地全文:下载
  • 作者:Svetlana Markova ; Tsutomu Nakamura ; Hiroo Makimoto
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2007
  • 卷号:30
  • 期号:8
  • 页码:1481-1487
  • DOI:10.1248/bpb.30.1481
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:Glucocorticoids such as prednisolone are used for their anti-inflammatory properties. But there is evidence to suggest that under certain conditions, glucocorticoids have pro-inflammatory effects, for example, enhancement of IL-1β production. To date, it has been reported that IL-1β production intensity was associated with single nucleotide polymorphisms at positions −1470, −511, and −31 in the promoter region and at position 3954 in exon 5 of the IL-1 β gene. In the present study, it was examined whether these IL-1 β genotypes were associated with the suppressive effect of prednisolone on IL-1β production in human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS). A midrange concentration (10−6 M ) of prednisolone suppressed the LPS-induced increase in IL-1β mRNA expression and protein release, while higher concentrations (10−5 M , 10−4 M ) exhibited less suppression or had a synergistic stimulative effect on IL-1β production in certain subjects. Under treatment with 10−4 M prednisolone, the levels of IL-1β protein production stimulated by LPS in PBMC extracted from the subjects with the IL-1 β TT−31, TC−31, and CC−31 genotypes were suppressed to 6.0±3.4%, 31.4±57.0%, and 87.7±84.8%, respectively, of the level in prednisolone-untreated control cells (TT−31 vs. CC−31, p <0.05). Glucocorticoid-based anti-inflammatory therapy might be less effective in patients with the IL-1 β TC−31 and CC−31 genotypes than those with the TT−31 genotype.
  • 关键词:interleukin-1β;acute inflammation;prednisolone;genotype;lipopolysaccharide;peripheral blood mononuclear cell
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