IL-1beta genotype-related effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells under acute inflammation.
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.
Division of Clinical Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Svetlana
S
Markova
Tsutomu
T
Nakamura
Hiroo
H
Makimoto
Tomoki
T
Ichijima
Motohiro
M
Yamamori
Akiko
A
Kuwahara
Koichi
K
Iwaki
Kohshi
K
Nishiguchi
Noboru
N
Okamura
Katsuhiko
K
Okumura
Toshiyuki
T
Sakaeda
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000208:Acute Disease; D000328:Adult; D000483:Alleles; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011239:Prednisolone