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Pre-Clinical Studies

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Bone Marrow Transplantation volume 45, pages 1562–1571 (2010)Cite this article

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Abstract

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.

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Acknowledgements

We thank Lenaldo Branco Rocha (Confocal Microscopy Laboratory—School of Medicine of Ribeirão Preto) for technical assistance in confocal microscopy. Confocal microscopy was supported by grants from FAPESP (2004/08868-0). This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (FINEP) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

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  1. D F Godoi and C R Cardoso: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    D F Godoi & J C Voltarelli

  2. Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    C R Cardoso, D B Ferraz, P R Provinciatto & J S Silva

  3. Department of Biological Sciences, Federal University of Triangulo Mineiro, Uberaba, Minas Gerais, Brazil

    C R Cardoso

  4. Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    F Q Cunha

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  1. D F Godoi
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Correspondence to D F Godoi.

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Godoi, D., Cardoso, C., Ferraz, D. et al. Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease. Bone Marrow Transplant 45, 1562–1571 (2010). https://doi.org/10.1038/bmt.2010.6

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