Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model.
Dig Dis Sci
; 58(11): 3165-77, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23949641
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Enzima Conversora de Angiotensina
/
Enalaprilato
/
Interleucina-10
/
Colite
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos