Prolonged kidney allograft survival with promethazine.

The effects of promethazine hydrochloride have been investigated in a rabbit kidney allograft model. The drug was ineffective on its own, but if added to a protocol that induced partial suppression of rejection in 50% of recipients, its effect was dramatic. Allograft survival was prolonged from a control mean of 10.3 days to a mean of 26.3 days. One animal survived 2 1/2 months, and no other drug than promethazine was given after day 6. Promethazine and 6-methylprednisolone alone also prolonged allograft survival, but the results were significantly better if the recipient had been exposed to donor blood before grafting. The results suggest that promethazine is a useful adjuvant immunosuppressive drug. It could be beneficial in man.     

Effect of transfusion of donor on allograft survival

It has been reported by two European transplant centers that blood transfusion of cadaver donors with third-party blood prior to nephrectomy increases renal allograft survival rates by approximately 30% at 1 year. A retrospective analysis in our center was performed on 293 kidney recipients, 110 of whom received kidneys from untransfused donors. Actuarial analyses revealed no significant differences in graft survival rates between all nontransfused donor kidneys and all transfused donor kidneys. Considering only first transplant recipients, there was no difference in graft survival rates between nontransfused donor kidneys and transfused donor kidneys. In addition, when only preoperatively transfused recipients receiving first transplants were examined, there was no difference in graft survival rates between nontransfused donor kidneys and transfused donor kidneys. Animal studies were performed with (Lewis x Brown Norway)F1 (LBNF1) hybrid rat hearts transplanted heterotopically to the abdomens of Lewis rat recipients. Six LBNF1 heart grafts had a mean survival time of 8.0 +/- 1.1 days. Five LBNF1 rats received 2 ml of heparinized whole blood from Charles River (CD) rats 24 hr before heart transplantation to Lewis recipients. The transfused LBNF1 grafts had a mean survival time of 6.6 +/- 0.9 days. Therefore, donor blood transfusion does not appear to prolong graft survival in this retrospective human study or in the animal model.     

Prolonged skin allograft survival in Scid mice reconstituted with isogeneic bone marrow stem cell antigen-1-positive cells and thymus tissue

INTRODUCTION: Many studies indicate that tolerance induction is much more dependent on the maturation status of lymphocytes than the age of the animal. We hypothesized that direct persistent contact of bone marrow stem cells with graft alloantigen will result in tolerance to that antigen in the adult animal. MATERIAL AND METHODS: Severe combined immunodeficient mice (CB-17-Scid, H-2b) were reconstituted with isogeneic bone marrow stem cell antigen-1 (Sca-1)-positive cells and grafted with fetal thymus (BMSC-T), followed by transplant of allogeneic skin grafts from C57BL/6 (H-2d) mice. The control group include CB-17 non-Scid mice, CB-17-Scid mice, and CB-17 Scid mice pretransplanted with nonmodified isogeneic bone marrow cells and fetal thymus (BMC-T). RESULTS AND DISCUSSION: Skin allograft survival was significantly prolonged in the group pretransplanted with isogeneic BMSC-T compared the group of non-Scid mice and the group of Scid mice pretransplanted with BMC-T (59.6 days vs 7.1 days vs 11.7 days). In 2 of 10 mice pretransplanted with BMSC-T, the skin allografts transplanted immediately after BMSC-T survived for more than 100 days, but the third-party skin allografts transplanted at 100 days after BMSC-T transplant were rejected. The results suggest direct persistent contact of bone marrow Sca-1-positive cells with graft alloantigen may be a feasible approach to prolong allograft survival and induce tolerance in a small fraction of adult animals.     

Prolonged limb allograft survival with CD 40 costimulation blockade, T-cell depletion, and megadose donor bone-marrow transfusion

The purpose of this study was to determine the efficacy of a treatment regimen consisting of CD 40 costimulation blockade, T-cell depletion, and megadose donor bone marrow transfusion in the limb allograft model. C57Bl/6 mice underwent limb transplantation from Balb/c mice and received MR1 (anti-CD 40 ligand monoclonal antibody), and CD4(+) and CD8(+) T cell-depleting antibodies with and without 120 x 10(6) donor bone-marrow transfusion. Recipients treated only with antibodies showed rejection at 51.4+/-17 (mean+/-SEM) days, while those who also received donor bone marrow had allograft survival of 67+/-16.4 days, with a range up to 91 days. Treated specimens with rejection had less lymphocytic infiltration than untreated controls. Recipients of donor bone marrow also demonstrated early mixed chimerism, which disappeared after 1 month. While allograft survival was prolonged, tolerance was not achieved, and the mechanism of rejection was more consistent with a chronic process.