Reappraisal of total body irradiation followed by bone marrow transplantation as a therapy for inflammatory bowel disease

Autor(es)

Godoi, Dannielle Fernandes ^[1] ; Cardoso, Cristina Ribeiro ^[2] ; Barbosa Silva, Marcelo Jose ^[3] ; Ferraz, Denise Brufato ^[4] ; Provinciatto, Pauline Rossetti ^[4] ; Cunha, Fernando de Queiroz ^[5] ; da Silva, Joao Santana ^[4] ; Voltarelli, Julio Cesar ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Uberlandia, Inst Ciencias Biomed, BR-38400 Uberlandia, MG - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Immunobiology; v. 218, n. 3, p. 317-324, MAR 2013.
• Citações Web of Science: 3

Resumo

The main current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated inflammation in the gut. Although these therapies have been successful, they are not curative and it is not possible to predict whether a beneficial response will occur or which patients will be refractory to the treatment. Total body irradiation (TBI) associated with chemotherapy is the first choice in the treatment of some hematological disorders and is an applicable option in the preparation of patients with hematologic diseases for hematopoietic stem cell transplantation. Then, in this study we investigated the association of TBI as immunosuppressive therapy and bone marrow cell (BMC) transplantation as a strategy to induce colitis recovery and immune reconstitution in the TNBS model of intestinal inflammation. TNBS mice treated with TBI associated with BMC transplantation presented elevated gain of weight and an overall better outcome of the disease when compared to those treated only with TBI. In addition, TBI associated or not with BMC reduced the frequency of inflammatory cells in the gut and restored the goblet cell counts. These results were accompanied by a down regulation in the production of inflammatory cytokines in the colon of mice treated with TBI alone or in association with BMC transplantation. The BMC infused were able to repopulate the ablated immune system and accumulate in the site of inflammation. However, although both treatments (TB! or TBI + BMC) were able to reduce gut inflammation, TBI alone was not enough to fully restore mice weight and these animals presented an extremely reduced survival rate when their immune system was not promptly reconstituted with BMC transplantation. Finally, these evidences suggest that the BMC transplantation is an efficient strategy to reduce the harmful effects of TBI in the colitis treatment, suggesting that radiotherapy may be an important immunosuppressive therapy in patients with IBD, by modulating the local inflammatory response. (C) 2012 Elsevier GmbH. All rights reserved. (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