Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Autor(es)

Godoi, D. F. ^[1] ; Cardoso, C. R. ^{[2, 3]} ; Ferraz, D. B. ^[3] ; Provinciatto, P. R. ^[3] ; Cunha, F. Q. ^[4] ; Silva, J. S. ^[3] ; Voltarelli, J. C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Internal Med, BR-25011405 Sao Paulo - Brazil

^[2] Univ Fed Triangulo Mineiro, Dept Biol Sci, Uberaba, MG - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-25011405 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-25011405 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BONE MARROW TRANSPLANTATION; v. 45, n. 10, p. 1562-1571, OCT 2010.
• Citações Web of Science: 4

Resumo

Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4(+) leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8(+) cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD. Bone Marrow Transplantation (2010) 45, 1562-1571; doi:10.1038/bmt.2010.6; published online 15 March 2010 (AU)

• Processo FAPESP: 04/08868-0 - Consolidação do Centro de Microscopia Funcional do Campus da USP/ Ribeirão Preto
• Beneficiário: Roy Edward Larson
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários