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 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.
Pakkala
I
I
Transplantation Laboratory, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland.
Taskinen
E
E
Pakkala
S
S
Räisänen-Sokolowski
A
A
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D008099:Liver / Q000473:pathology; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000473:pathology
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002117:Calcitriol