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Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model.

ABSTRACT: 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.We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model.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.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.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.

SUBMITTER: Sueyoshi R

PROVIDER: S-EPMC3859685 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model.

Sueyoshi Ryo R Ignatoski Kathleen M Woods KM Daignault Stephanie S Okawada Manabu M Teitelbaum Daniel H DH

Digestive diseases and sciences 20130815 11

<h4>Background</h4>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.<h4>Aim</h4>We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model.<h4>Methods</h4>Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.) fo ...[more]

PMID: 23949641

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Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model.

Publications

Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model.

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