PROLACTIN SUPPRESSION ENHANCES THE EFFECTS OF PERIOPERATIVE DONOR-SPECIFIC BLOOD-TRANSFUSIONS ON GRAFT-SURVIVAL

The induction of donor-specific unresponsiveness in allograft recipien ts would lessen the need for chronic immunosuppression and its concomi tant morbidities. In view of recognized interactions between the immun e and neuroendocrine systems, we hypothesized that manipulating prolac tin (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 pitu itary 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 d irect effects on lymphoid cells in vitro. BR had no effects on graft s urvival 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 a ffect 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 une quivocally prolonged graft survival (17.0 +/- 1.4 days; P < 0.01 vs al l controls), suggesting that hypoprolactinemia increased the tolerogen ic effects of DST. Spleen and lymph node cells harvested from BR-DST-C sA 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. (C) 19 96 Academic Press, Inc.