PARTIAL INHIBITION OF ALLOGRAFT ARTERIOSCLEROSIS (CHRONIC REJECTION) BY 15-DEOXYSPERGUALIN

15-deoxyspergualin (DSG) is an immunosuppressive drug that suppresses monocyte/macrophage function and/or T cell induction and early differe ntiation of B lymphocytes. It is as effective as cyclosporine in the p revention of acute rejection. We have investigated the effects of DSG on rat aortic allograft arteriosclerosis (chronic rejection). DSG was administered to the recipient rat at a dose of 0.3-10 mg/kg/day i.p. f or 1-3 months, after which recipients were sacrificed. Histological ch anges were quantitated from paraffin sections. DSG is effective in chr onic rejection in rat aortic allografts and reduces all three manifest ations in the vascular wall-adventitial inflammation, media necrosis, and intimal thickening. At the dose of 1.0 mg/kg/day we demonstrated s ignificant inhibition of adventitial inflammation from 10.6 point scor e units (psu) to 4.7 psu (P<0.05), of media necrosis (P=0.004) and of intimal thickening from 2.9 psu to 0.8 psu (P=0.008). The therapeutic window was small in the long-term experiment. Doses of 3-10 mg/kg/day were toxic and 0.3 mg/kg/day was ineffective. In vitro smooth muscle c ell proliferation was not inhibited by DSG and in the in vivo carotic denudation model DSG had no inhibitory effects either. These results s uggest that DSG works via suppression of the immune/inflammatory respo nse rather than via a direct antiproliferative effect on smooth muscle cells.