MC 1288--a vitamin D analogue with immunosuppressive effects on heart and small bowel grafts.
The vitamin D analogue MC 1288 (20-epi-1 alpha,25-dihydroxycholecalciferol) was tested here for its possible immunosuppressive properties in vivo using different rat transplantation models. MC 1288, in a dose of 0.1 microgram/kg daily, administered intraperitoneally for 10 days, was found 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 immunostimulatory 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 into 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, while 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 that may make it suitable for the prevention of graft rejection.
Johnsson
C
C
Department of Transplantation Surgery, University Hospital, Uppsala, Sweden.
Tufveson
G
G
D000276:Adjuvants, Immunologic; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006087:Graft vs Host Reaction / Q000187:drug effects; D016027:Heart Transplantation; D006820:Hyaluronic Acid / Q000032:analysis; D006912:Hydroxyquinolines / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000737:chemistry; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D014184:Transplantation, Homologous
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; D007166:Immunosuppressive Agents; C045282:roquinimex; D006820:Hyaluronic Acid; D002117:Calcitriol