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Graft-Versus-Host Disease

MC1288, a vitamin D analog, prevents acute graft-versus-host disease in rat bone marrow transplantation

Bone Marrow Transplantation volume 27, pages 863–867 (2001)Cite this article

Abstract

The major obstacle to successful bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Vitamin D analogs have shown their efficacy in solid organ transplantation. The purpose of this study was to investigate the suitability of a novel vitamin D analog, MC1288, in the prevention of acute GVHD in a rat BMT model. Allogeneic BMT were performed from Lewis to BN rats (n = 18). The animals were divided into four groups: an untreated control group, MC1288, cyclosporin A (CsA), and MC1288 + CsA-treated groups. Rats were harvested for histology and immunohistochemistry on day 20 after BMT. Histological changes for GVHD in liver, skin, and spleen were scored. Positivity in immunostaining was quantified as the number of positive cells/high power field. Treatment with MC1288 decreased clinical signs of GVHD compared with untreated or CsA-treated rats. Histological manifestations of GVHD, expressed as mean total increment, were significantly lower (1.4 ± 0.5) in MC1288 than in untreated (5.0 ± 1.6) or CsA (3.5 ± 1.0) groups. Combining MC1288 and CsA further improved histology (1.1 ± 0.6). The expression of CD4, CD8, MHC class II, interleukin-2 receptor, nitric oxide 2, and NKR-P1A (NK cells) positivity was significantly decreased in the liver and skin of BMT rats by MC1288. MC1288 was effective in preventing clinical and histological signs and symptoms of GVHD. This novel vitamin D analog could be used as an immunomodulating agent in BMT. Bone Marrow Transplantation (2001) 27, 863–867.

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Acknowledgements

We wish to acknowledge the excellent technical assistance of M Anttila RN and T Lahtinen RN, and Roderick Dixon, BA for reviewing the English language. This study was supported by the Finnish Medical Society Duodecim, the Ida Montin Foundation, Helsinki, and the Helsinki University Central Hospital Foundation.

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  1. Transplantation Laboratory, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland

    I Pakkala, E Taskinen, S Pakkala & A Räisänen-Sokolowski

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  1. I Pakkala
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Pakkala, I., Taskinen, E., Pakkala, S. et al. MC1288, a vitamin D analog, prevents acute graft-versus-host disease in rat bone marrow transplantation. Bone Marrow Transplant 27, 863–867 (2001). https://doi.org/10.1038/sj.bmt.1702873

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