Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model
R Sueyoshi, KMW Ignatoski, S Daignault… - Digestive diseases and …, 2013 - Springer
R Sueyoshi, KMW Ignatoski, S Daignault, M Okawada, DH Teitelbaum
Digestive diseases and sciences, 2013•SpringerBackground 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 (PO) for 14 days. The ACE-I enalaprilat was …
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 (PO) for 14 days. The ACE-I enalaprilat was …
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.
Springer
以上显示的是最相近的搜索结果。 查看全部搜索结果