A vitamin D analog, MC1288, inhibits adventitial inflammation and suppresses intimal lesions in rat aortic allografts.
Certain analogs of vitamin D have been shown to prevent autoimmune diseases and prolong cardiac allograft survival. We transplanted aortic allografts from DA rats to WF rats to investigate the effect of a synthetic vitamin D analog, MC1288, and cyclosporine (CsA), alone or in combination, on acute and chronic rejection (allograft arteriosclerosis) and the mechanism of action of MC1288. The histological changes in the vascular wall were quantitated as point score units (psu). Adventitial inflammation linked with acute rejection at 1 month after transplantation decreased from 10.0+/-0.9 psu to 4.1+/-1.0 psu (P<0.01) when MC1288, 0.1 microg/kg/every other day, and CsA, 5 mg/kg/day, were combined. Intimal thickening decreased from 2.5+/-0.3 psu to 1.1+/-0.4 psu (P<0.05) at 3 months after transplantation. Proliferation of the adventitial lymphoid cells, detected by bromodeoxyuridine labeling, decreased from 140+/-36 to 20+/-19 labeled cells/cross-section. MC1288 alone suppressed interleukin 2 receptor-expressing cells from 156 to 90 positive cells/cross-section. Taken together, MC1288 with CsA effectively suppress T cell proliferation and activation and decrease intimal thickening.
Räisänen-Sokolowski
A K
AK
Transplantation Laboratory, University of Helsinki, Helsinki University Central Hospital, Finland.
Pakkala
I S
IS
Samila
S P
SP
Binderup
L
L
Häyry
P J
PJ
Pakkala
S T
ST
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D001018:Aortic Diseases / Q000276:immunology / Q000517:prevention & control*; D001161:Arteriosclerosis / Q000276:immunology / Q000517:prevention & control*; D016572:Cyclosporine / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006934:Hypercalcemia / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051381:Rats; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D014807:Vitamin D / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D014807:Vitamin D; D016572:Cyclosporine