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

• Published in: Biological & pharmaceutical bulletin 2007/08/01, Vol.30(8), pp.1481-1487
• Main Authors: Markova, Svetlana, Nakamura, Tsutomu, Makimoto, Hiroo, Ichijima, Tomoki, Yamamori, Motohiro, Kuwahara, Akiko, Iwaki, Koichi, Nishiguchi, Kohshi, Okamura, Noboru, Okumura, Katsuhiko, Sakaeda, Toshiyuki
• Format: Article
• Language: English
• Subjects: acute inflammation; genotype; interleukin-1β; lipopolysaccharide; peripheral blood mononuclear cell; prednisolone
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.30.1481

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-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