Peripheral regulatory T cells and serum transforming growth factor-ß: relationship with clinical response to infliximab in Crohn's disease.
Inflamm Bowel Dis
; 16(11): 1891-7, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20848485
BACKGROUND: CD4(+)Foxp3(+) regulatory T cells (Treg) inhibit T-cell proliferation in vitro and are effective in suppressing colitis in mouse models. Tumor necrosis factor (TNF)-α, which is centrally involved in Crohn's disease (CD) pathogenesis, also impairs Treg function. Here we investigated the influence of anti-TNF therapy on Treg frequency and function in CD. METHODS: Twenty CD patients were treated with infliximab administered at weeks 0, 2, and 6. Blood was collected immediately before the first infusion and after 10 weeks. Treg frequency was quantified by flow cytometry. Treg function was measured using a standard coculture assay. Serum levels of transforming growth factor (TGF)-ß1 and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Pretreatment Treg frequency and serum TGF-ß1 levels were significantly higher in nonresponder than responder patients. Clinical improvement in 12 CD patients was associated with a significant increase of Treg frequency after 10 weeks. Treg were functionally active before and after treatment with infliximab, both in responder and nonresponder CD patients. In responder patients the restoration of Treg pool was accompanied by a parallel significant increase of serum TGF-ß1 and IL-10. No significant change in the elevated Treg or serum TGF-ß1 was seen in nonresponder patients. CONCLUSIONS: This study suggests that there may be a relationship between numbers of Treg in the blood, serum TGF-ß1, and response to infliximab; however, further prospective studies are needed.
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Base de dados:
MEDLINE
Assunto principal:
Fármacos Gastrointestinais
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Doença de Crohn
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Fator de Crescimento Transformador beta
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Linfócitos T Reguladores
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Anticorpos Monoclonais
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article