Intestinal allograft survival in the rat following pretreatment with donor-specific UV-B-irradiated leukocytes and peritransplant immunosuppression with cyclosporine.
Previous studies from our laboratory showed that pretreatment with ultraviolet-B-irradiated donor leukocytes (UV-B DL) combined with brief peritransplant cyclosporine (CyA) resulted in indefinite survival of Wistar/Furth rat cardiac allografts in Lewis recipients. This study was designed to examine the effect of pretransplant UV-B DL with or without peritransplant CyA on orthotopic intestinal allografts in the same rat strain combination. The results showed that while low-dose CyA treatment alone (10 mg/kg i.m. on days 0, +1, and +2) had no effect on intestinal allograft rejection, 20 mg/kg (on days 0, +1, and +2) CyA significantly (P less than or equal to 0.001) prolonged graft survival, with 33% of the hosts surviving indefinitely. The highest dose of CyA (30 mg on days 0, +1, and +2) abrogated rejection, but most transplant recipients succumbed to infection and functional ileus due to a toxic side effect of CyA. Pretreatment with UV-B DL on days -14 and -7 alone did not prolong intestinal allograft survival. Combination of a subtherapeutic CyA dose (20 or 10 mg/kg) given on days 0, +1, and +2 with pretransplant UV-B DL on days -14 and -7 did not alter the survival of intestinal allografts compared to treatment with CyA alone. This suggests that pretreatment with UV-B DL with or without peritransplant administration of CyA has no effect on intestinal allograft survival, in contrast to the effect of such combined treatment on cardiac allograft survival, where indefinite graft survival is observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Gundlach
M
M
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Oluwole
S F
SF
D'Agati
V
V
Hardy
M A
MA
D000818:Animals; D001803:Blood Transfusion; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000276:immunology / Q000528:radiation effects; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous; D014466:Ultraviolet Rays
D016572:Cyclosporine