Donor-specific immunosuppression is important in transplant surgery. We examined the effect of intraportal donor-specific bone marrow transplantation on heterotopic small bowel transplantation in the high responder rat combination, ACI to Lewis. The study comprised five treatment groups: untreated controls (group 1); FK506 alone (group 2); low-dose predonine + FK506 (group 3); high-dose predonine + FK506 (group 4); and intraportal donor-specific bone marrow transplantation + FK506 (group 5). Intraportal transplantation was performed pre-operatively and FK506 and predonine given post-operatively. Intestinal allograft survival and changes of intragraft cytokine expression were analysed using the reverse transcription polymerase chain reaction. Allograft survival (mean ± SD) was lowest in group 1 and greatest in group 5. The group 5 treatment regimen also down-regulated interferon-γ and interleukin-2 transcription in the transplanted intestine. Intraportal donor bone marrow transplant combined with FK506 immunosuppression was found therefore to be the most beneficial treatment regimen
SchrautWH: Current status of small bowel transplantation. Gastroenterology1988; 94: 525–533.
2.
TzakisAGTodoSReyesJNourBAbu-ElmagdKSelbyR: Intestinal transplantation in children under FK506 immunosuppression. J Pediatr Surg1993; 28: 1040–1043.
3.
MuraseNDemetrisAJWooJTanabeMFuruyaTTodoS: Graft-versus-host disease after Brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK506. Transplantation1993; 55: 1–7.
4.
ReyesJBuenoJKocoshisSGreenMAbu-ElmagdKFurukawaH: Current status of intestinal transplantation in children. J Pediatr Surg1998; 33: 243–254.
5.
TodoSTzakisAGAbu-ElmagdKReyesJFungJJCasavillaA: Cadaveric small bowel and small bowel/liver transplantation in humans. Transplantation1992; 53: 369–376.
6.
TodoSTzakisAAbu-ElmagdKReyesJStarzlTE: Current status of intestinal transplantation. Adv Surg1994; 27: 295–316.
7.
GruessnerRSharpHL: Living-related intestinal transplantation: first report of a standardized surgical technique. Transplantation1997; 64: 1605–1607.
8.
MadsenKLYancharNLSigaletDLReigelTFedorakRN: FK506 increases permeability in the intestine by inhibiting mitochondrial function. Gastroenterology1995; 109: 107–114.
9.
SigaletDLWilliamsDCGarolaRThornePMartinG: Impact of FK506 and steroids on adaptation after intestinal resection or segmental transplantation. Pediatr Transplant2000; 4: 12–20.
10.
FauciAS: Immunosuppressive and anti-inflammatory effects of glucocorticoids. In: Glucocorticoid Hormone Action (BaxterJGRousseauG, eds). New York: Springer Publishing Co Inc., 1979; pp449–465.
11.
BeatoM: Gene regulation by steroid hormones. Cell1989; 56: 335–344.
12.
NakaoAKobayashiEShenSDYoshinoTTanakaN: Impact of tacrolimus and bone marrow augmentation on intestinal allograft survival and intragraft cytokine expression. J Med2001; 32: 207–230.
13.
KobayashiEKamadaNEnosawaSToyamaNDelriviereLGotoS: Comparison of potentiality to induce graft-versus-host reaction with small bowel, pancreas/spleen, and liver transplantation in the rat. Clin Exp Immunol1993; 92: 527–531.
14.
LerutJPCiccarelliOMauelEGheerardhynRTalpeSSempouxC: Adult liver transplantation and steroid-azathioprine withdrawal in cyclosporine-based immunosuppression − 5 year results of a prospective study. Transpl Int2001; 14: 420–428.
15.
NakanoYMondenMValdiviaLAGotohMTonoTMoriT: Permanent acceptance of liver allografts by intraportal injection of donor spleen cells in rats. Surgery1992; 111: 668–676.
16.
YoshimuraNMatsuiSHamashimaTLeeCJOhsakaYOkaT: The effects of perioperative portal venous inoculation with donor lymphocytes on renal allograft survival in the rat. I. Specific prolongation of donor grafts and suppressor factors in the serum. Transplantation1990; 49: 167–171.
17.
GorczynskiRMChanZChungSCohenZLevyGSullivanB: Prolongation of rat small bowel or renal allograft survival by pretransplant transfusion and/or by varying the route of allograft venous drainage. Transplantation1994; 58: 816–820.
18.
SugiuraKKatoKHashimotoFJinTAmohYYamamotoY: Induction of donor-specific T cell anergy by portal venous injection of allogenic cells. Immunobiology1997; 197: 460–477.
19.
PerezRVSwansonCMorganMEricksonKHubbardNEGermanJB: Portal venous transfusion upregulates Kupffer cell cyclooxygenase activity: a mechanism of immunosuppression in organ transplantation. Transplantation1997; 64: 135–139.
20.
GorczynskiRMChenZHoangYRossi-BergmanB: A subset of gamma delta T-cell receptor-positive cells produce T-helper type-2 cytokines and regulate mouse skin graft rejection following portal venous pretransplant preimmunization. Immunology1996; 87: 381–389.
21.
IshidoNMatsuokaJMatsunoTNakagawaKTanakaN: Induction of donor-specific hyporesponsiveness and prolongation of cardiac allograft survival by jejunal administration of donor splenocytes. Transplantation1999; 68: 1377–1382.
22.
McDiarmidSVFarmerDGKuniyoshiJSRobertMKhadaviAShakedA: The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation. Transplantation1994; 58: 690–697.
23.
MadaraJLStaffordJ: Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest1989; 83: 724–727.
24.
SuGLWalgenbachKJHeecktPHWangQHalfterWWhitesideTL: Increased expression of interferon-gamma in a rat model of chronic intestinal allograft rejection. Transplantation1996; 62: 242–248.
25.
NathanCFMurrayHWWiebeMERubinBY: Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med1983; 158: 670–689.
26.
YamamotoMFujihashiKBeagleyKWMcGheeJRKiyonoH: Cytokine synthesis by intraepithelial lymphocytes. Both gamma/ delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5. J Immunol1993; 150: 106–114.
27.
MonacoAP: Strategies for induction of clinical tolerance. Transplant Proc2001; 33: 51–56.
28.
LevyAEAlexanderJW: The significance of timing of additional short-term immunosuppression in the donor-specific transfusion/cyclosporine-treated rat. Transplantation1996; 62: 262–266.
29.
ContiFDoussetBArchambeauDLouvelAHoussinDCalmusY: Enhanced risk of steroid—resistant acute rejection following pretransplant steroid therapy in liver graft recipients. Transplantation1995; 60: 1104–1108.
30.
KoshibaTVan DammeBJiPLuYSefriouiHOverberghL: Addition of steroids blocks the tolerogenic potential of donor-specific blood transfusion. Transplant Proc2001; 33: 375–376.
