Effect of Deoxyspergualin on Vascular Rejection in Canine Kidney Transplantation

Abstract

Deoxyspergualin (DSG), an analogue of spergualin produced by Bacillus laterosporus, has a strong immunosuppressive effect in various transplantation models. In this study, we investigated the effect of DSG on vascular rejection in canine kidney transplantation.To enhance vascular rejection, donor-specific blood transfusion (DST) was carried out on days 28, 21 and 14 preceding kidney transplantation. After DST, the donor kidney was transplanted to the recipient iliac fossa. The recipient animals were divided into five groups: namely, Group 1 (n = 7), no treatment; Group 2 (n = 6), DST only; Group 3 (n = 5), DSG only (treated with DSG intravenously at 1.2 mg./kg./day for the first 3 days after transplantation, 1.0mg./kg./day for the following 3days and 0.8mg./kg./day for the following 8 days); Group 4 (n = 6), DST and DSG treatment (same protocol as Group 3); and Group 5 (n = 5), DST and cyclosporine (CsA) (treated with CsA orally at 10mg./kg./day for 14days after transplantation).In Group 2, DST treatment significantly reduced kidney graft survival time (8.6 ± 2.2 days) compared with Group 1 (14.1 ± 5.5 days). Despite DST, DSG treatment (Group 4) significantly prolonged graft survival time (29.5 ± 2.6 days), whereas treatment with CsA (Group 5) did not prolong survival time (14.1 ± 5.5 days) (Group 4 versus 5, p < 0.01).The onset of rejection was significantly delayed in Group 4 (22.1 ± 2.7 days) compared with Groups 2 (5.7 ± 2.4 days) and 5 (13.0 ± 5.7 days) (p < 0.01). In contrast, the interval between rejection onset and animal death was significantly reduced in Groups 2 (3.0 ± 0.6 days) and 5 (2.4 ± 1.0 days) compared with Group 4 (7.3 ± 1.7 days) (p < 0.01). These findings suggest that DSG successfully prevented humoral-type (accelerated acute-type) rejections.Histologically, nonDST groups (Groups 1 and 3) showed minimum vascular rejection. In contrast, all recipients in Group 2 showed severe vascular rejection, as did 80% of CsA treated-animals (Group 5). Despite DST, however, 84% of DSG treated-animals (Group 4) showed minimal or mild vascular rejection and only 17% had severe rejection (Group 4 versus 5, p < 0.04).These data suggest that both clinically and histologically, DSG has more potent immunosuppressive effects against humoral and vascular rejection than CsA.