IL-1β Genotype-Related Effect of Prednisolone on IL-1β Production in Human Peripheral Blood Mononuclear Cells under Acute Inflammation(Pharmacology)

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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-lft 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-1β gene. In the present study, it was examined whether these IL-1β 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-1β 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-1β TC^<-31> and CC^<-31> genotypes than those with the TT^<-31> genotype.
社団法人日本薬学会の論文
2007-08-01

IL-1β Genotype-Related Effect of Prednisolone on IL-1β Production in Human Peripheral Blood Mononuclear Cells under Acute Inflammation(Pharmacology)

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