Prolactin Suppression Enhances the Effects of Perioperative Donor-Specific Blood Transfusions on Graft Survival

Abstract

The induction of donor-specific unresponsiveness in allograft recipients would lessen the need for chronic immunosuppression and its concomitant morbidities. In view of recognized interactions between the immune and neuroendocrine systems, we hypothesized that manipulating prolactin (PRL) levels might enhance the immunosuppressive effects of donor-specific blood transfusions. Bromocriptine (BR) and domperidone (DOM), administered via osmotic pumps, were used to inhibit or increase pituitary PRL secretion, respectively, in male LEW rats treated with donor-specific transfusions (DST, Day −1), cyclosporine (CsA, 5 mg/kg, Days −1 to +1), and receiving ACI heart allografts. Neither compound had direct effects on lymphoid cellsin vitro.BR had no effects on graft survival in rats treated with either BT or CsA (BR–DST, 7.0 ± 0.7; BR–CsA, 9.2 ± 3.1; CsA, 11.3 ± 3.9 days). DOM–DST–CsA also did not affect graft survival (8.7 ± 3.1 days). BR and CsA, similarly, had no effects in rats receiving a nonspecific transfusion (8.8 ± 1.1 days). In contrast, BR administration in rats treated with DST and CsA unequivocally prolonged graft survival (17.0 ± 1.4 days;P< 0.01 vs all controls), suggesting that hypoprolactinemia increased the tolerogenic effects of DST. Spleen and lymph node cells harvested from BR–DST–CsA rats on Postoperative Day 8 showed impaired responses to mitogenic or allogeneic challenges. Cytotoxic antibody levels at Day 5 were low in all groups receiving CsA. Possible mechanisms are discussed.