MC-1288 - A VITAMIN-D ANALOG WITH IMMUNOSUPPRESSIVE EFFECTS ON HEART AND SMALL-BOWEL GRAFTS

The vitamin D analogue MC 1288 (20-epi-1alpha,25-dihydroxycholecalcife rol) was tested here for its possible immunosuppressive properties in vivo using different rat transplantation models. MC 1288, in a dose of 0.1 mug/kg daily, administered intraperitoneally for 10 days, was fou nd to be effective in prolonging cardiac allograft survival. Untreated recipients rejected their grafts around day 8 while MC 1288 treatment delayed rejection until day 22 (P < 0.001). Addition of the immunosti mulatory drug LS-2616 (Linomide) reduced the immunosuppressive effect of MC 1288 and rejection occurred around day 11. The immunosuppressive effect of MC 1288 on rejection following small bowel transplantation was determined by measuring the amounts of hyaluronan (HA) secreted in to the intestinal lumen. On day 6 post-transplantation the amounts of intraluminal HA in untreated animals was 29.2 +/- 5.3 ng/min and cm, w hile in MC 1288-treated animals it was just 5.0 +/- 1.6 ng/min and cm (P < 0.01). We conclude that MC 1288 has immunosuppressive effects tha t many make it suitable for the prevention of graft rejection.