Impact of tacrolimus and bone marrow augmentation on intestinal allograft survival and intragraft cytokine expression in rats.
Effects of simultaneous bone marrow transplantation (BMT) with a short course of tacrolimus on a heterotopic small bowel transplantation (SBT) were tested in a high responder rat combination of ACI (RT1avl) to LEW (RTIl). Intestinal allograft survival and changes of intragraft cytokine expression by this treatment were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Only the treatment with donor specific BMT via portal vein plus a short course of tacrolimus (1.0 mg/Kg for 3 days) significantly prolonged allograft survival (mean +/- SD; 11.7 +/- 1.9 days), while the grafts were rejected at 4 to 8 days by other control treatments. More beneficial effect of donor type BMT via portal vein on allograft survival was achieved (19.0 +/- 2.2 days) by containing administration of a lower dose of tacrolimus (0.5 mg/Kg for 11 days). Both gene expression of IFN-gamma and infiltration of IFN-gamma-producing cells were strongly suppressed by this protocol, while tacrolimus treatment alone could not suppress IFN-gamma production. Tacrolimus treatment added with donor specific BMT down-regulated IL-12 and IFN-gamma transcript, resulted in a significant prolongation of intestinal allograft survival.
Nakao
A
A
First Department of Surgery, Okayama University Medical School, Japan.
Kobayashi
E
E
Shen
S D
SD
Yoshino
T
T
Tanaka
N
N
D000818:Animals; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000235:genetics; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous
D016207:Cytokines; D007166:Immunosuppressive Agents; D018664:Interleukin-12; D007371:Interferon-gamma; D016559:Tacrolimus