スエヨシ　リヨウ   末吉　亮    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model.
掲載誌名	正式名：Digestive diseases and sciences 略　 称：Dig Dis Sci ISSNコード：15732568/01632116
掲載区分	国外
巻・号・頁	58(11),pp.3165-3177
著者・共著者	Sueyoshi Ryo†, Ignatoski Kathleen M Woods, Daignault Stephanie, Okawada Manabu, Teitelbaum Daniel H
担当区分	筆頭著者
発行年月	2013/11
概要	BACKGROUND:We previously demonstrated angiotensin converting enzymes (ACE) over-expression in a dextran-sodium sulfate colitis model; ACE inhibitor (ACE-I) treatment reduced colitis severity in this model. However, ACE-I has not been tested in more immunologically relevant colitis models.AIM:We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model.METHODS:Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.) for 14 days. The ACE-I enalaprilat was given transanally at a dose of 6.25 mg/kg for 21 days. Prednisolone (PSL) with or without enalaprilat were used as therapeutic, comparative groups. All groups were compared to a placebo treated group. Outcome measures were clinical course, histology, abundance of pro-inflammatory cytokines/chemokines, and epithelial barrier function.RESULTS:Enalaprilat exhibited better survival (91 %) versus other treatment groups (PSL: 85.7 %, PSL + ACE-I: 71.4 %, placebo: 66.6 %). The ACE-I and PSL + ACE-I groups showed significantly better histological scores versus placebo mice. ACE-I and the PSL groups significantly reduced several pro-inflammatory cytokines versus placebo mice. FITC-dextran permeability was reduced in the ACE-I and PSL + ACE-I groups. Blood pressure was not affected in ACE-I treated mice compared to placebo mice.CONCLUSIONS:ACE-I was effective in reducing severity of colitis in an IL-10-/- model. The addition of prednisolone minimally augmented this effect. The findings suggest that appropriately dosed ACE-I with or without steroids may be a new therapeutic agent for colitis.
DOI	10.1007/s10620-013-2825-4
PMID	23949641