IL-1beta genotype-related effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells under acute inflammation |
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Authors: | Markova Svetlana Nakamura Tsutomu Makimoto Hiroo Ichijima Tomoki Yamamori Motohiro Kuwahara Akiko Iwaki Koichi Nishiguchi Kohshi Okamura Noboru Okumura Katsuhiko Sakaeda Toshiyuki |
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Affiliation: | Division of Clinical Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. |
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Abstract: | 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-1beta production. To date, it has been reported that IL-1beta 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-1beta gene. In the present study, it was examined whether these IL-1beta genotypes were associated with the suppressive effect of prednisolone on IL-1beta 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-1beta 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-1beta production in certain subjects. Under treatment with 10(-4) M prednisolone, the levels of IL-1beta protein production stimulated by LPS in PBMC extracted from the subjects with the IL-1beta 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-1beta TC(-31) and CC(-31) genotypes than those with the TT(-31) genotype. |
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