Deoxyspergualin delays xenograft rejection in the guinea pig-to-C6-deficient rat heart transplantation model

This study aimed to investigate the effects of 15-deoxyspergualin (DSG), ta crolimus (FK 506) and cyclosporin A (CyA), alone or in combination, on dela yed xenograft rejection (DXR). We used the guinea-pig-to-C6-deficient (C6(- ))-PVG-rat heart transplantation model, since in this strain combination, h yperacute rejection is avoided. In C6(-) control rats, the guinea pig xenog rafts survived for 39.2 +/- 6.3 h (mean +/- SD). Splenectomy alone resulted in a xenograft survival of 71.8 +/- 7.8 h, but the addition of CyA or FK 5 06 did not further improve graft survival (73.6 +/- 3.0 h and 72.0 +/- 17.6 h, respectively). In contrast, DSG treatment increased graft survival to a mean of 99.8 +/- 9.2 h. When CyA or FK 506 was combined with DSG, no addit ional effects were observed (105 +/- 24.3 h and 95.1 +/- 5.6 h, respectivel y). DSG alone or in combination with FK 506 or CyA resulted in a significan t reduction in the serum IgM levels and reduced the deposits of IgM and IgG in rejected grafts. However, all xenografts were still heavily infiltrated by EDI + macrophages, regardless of the treatment used. Thus, DSG treatmen t resulted in moderate prolongation of xenograft survival in C6(-) rats. Th e effect seems to be related to suppression of xenoreactive antibody produc tion. To prolong xenograft survival further, strategies that inhibit macrop hage infiltration seem required.