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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Johnsson C, Tufveson G . MC 1288 – a vitamin D analogue with immunosuppressive effects on heart and small bowel grafts Transplant Int 1994 7: 392–397
Johnsson C, Binderup L, Tufveson G . The effects of combined treatment with the novel vitamin D analogue MC 1288 and cyclosporine A on cardiac allograft survival Transplant Immunol 1995 3: 245–250
Kallio E, Hayry P, Pakkala S . MC1288, a vitamin D analogue, reduces short- and long-term renal allograft rejection in the rat Transplant Proc 1996 28: 3113
Hullett DA, Cantorna MT, Redaelli C et al. Prolongation of allograft survival by 1,25-dihydroxyvitamin D3 Transplantation 1998 66: 824–828
Casteels K, Waer M, Laureys J et al. Prevention of autoimmune destruction of syngeneic islet grafts in spontaneously diabetic nonobese diabetic mice by a combination of a vitamin D3 analog and cyclosporine Transplantation 1998 65: 1225–1232
Mathieu C, Laureys J, Waer M, Bouillon R . Prevention of autoimmune destruction of transplanted islets in spontaneously diabetic NOD mice by KH1060, a 20-epi analog of vitamin D: synergy with cyclosporine Transplant Proc 1994 26: 3128–3129
Raisanen-Sokolowski AK, Pakkala IS, Samila SP et al. A vitamin D analog, MC1288, inhibits adventitial inflammation and suppresses intimal lesions in rat aortic allografts Transplantation 1997 63: 936–941
Pakkala I, Savli H, Knuutila S et al. CB1093, a novel vitamin D analog; effects on differentiation and clonal growth on HL-60 and de novo leukemia cells Leukemia Res 1997 21: 321–326
Koeffler H, Hirji K, Itri L, Group SCL . 1,25-Dihydroxyvitamin D3: in vivo and in vitro effects on human preleukemic and leukemic cells Cancer Treat Rep 1985 69: 1399–1407
Pakkala S, de Vos S, Elstner E et al. Vitamin D3 analogs: effect on leukemic clonal growth and differentiation, and on serum calcium levels Leukemia Res 1995 19: 65–72
Renkonen R, Hayry P . Bone marrow transplantation in the rat. I. Histologic correlations and quantitation of cellular infiltrates in acute graft-versus-host disease Am J Pathol 1984 117: 462–470
Lerner KG, Kao GF, Storb R et al. Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors Transplant Proc 1974 6: 367–371
Slavin RE, Santos GW . The graft versus host reaction in man after bone marrow transplantation: pathology, pathogenesis, clinical features, and implication Clin Immunol Immunopathol 1973 1: 472–498
Sale GE, Lerner KG, Barker EA et al. The skin biopsy in the diagnosis of acute graft-versus-host disease in man Am J Pathol 1977 89: 621–635
Krenger W, Hill GR, Ferrara JL . Cytokine cascades in acute graft-versus-host disease Transplantation 1997 64: 553–558
Nikolic B, Lee S, Bronson R et al. Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets J Clin Invest 2000 105: 1289–1298
Elstner E, Lee YY, Hashiya M et al. 1 alpha,25-Dihydroxy-20-epi-vitamin D3: an extraordinarily potent inhibitor of leukemic cell growth in vitro Blood 1994 84: 1960–1967
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702873
Keywords
This article is cited by
-
Vitamin D: is it important in haematopoietic stem cell transplantation? A review
Bone Marrow Transplantation (2019)
-
Whole-Body UVB Irradiation during Allogeneic Hematopoietic Cell Transplantation Is Safe and Decreases Acute Graft-versus-Host Disease
Journal of Investigative Dermatology (2012)
-
Course of serum 25-hydroxyvitamin D3 status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation
Annals of Hematology (2012)
-
Effect of vitamin D treatment in chronic GVHD
Bone Marrow Transplantation (2011)
-
Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia
Leukemia (2009)