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

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 a cute GVHD in a rat BMT model. Allogeneic BMT were performed from Lewis to B N rats (n = 18). The animals were divided into four groups: an untreated co ntrol 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 c ompared 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 exp ression 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 c ould be used as an immunomodulating agent in BMT.