Anti-inflammatory effects of ischemic preconditioning on rat small bowel allografts.

ABSTRACT

INTRODUCTION: Minimizing the inflammatory events that follow intestinal transplantation may influence immediate graft function and improve outcome. Ischemic preconditioning (IPc) has been shown to ameliorate early inflammatory responses, and it may also attenuate the potentially damaging inflammation after intestinal transplantation. Herein, we examine the influence of intestinal IPc on inflammatory indices (tissue expression of ICAM-1, CD11a, and CD44 and serum levels of the soluble ICAM-1, sICAM-1) after heterotopic intestinal transplantation. METHODS: Lewis rats received full-length preconditioned or non-preconditioned Brown Norway intestinal allografts in the absence of immunosuppression. Preconditioned grafts were subjected to 1 cycle of 10 minutes of ischemia-reperfusion. Preconditioned and non-preconditioned isografts acted as controls. Blood was collected on alternate days post-transplant, and graft tissue harvested on sacrifice. ICAM-1, CD44, and CD11a expression was determined by immunohistochemistry, and the area of staining was quantified using image analysis. Serum soluble ICAM-1 levels were determined using an R&D Systems Quantikine enzyme immunoassay. RESULTS: (1) IPc ameliorated serum levels of sICAM-1 until severe rejection (day 7) overcame this down-regulation when compared to non-preconditioned allografts (day 3 34,304 vs 40,479 pg/mL; day 5 52,441 vs 61,593 pg/mL; day 7 75,114 vs 73,309 pg/mL; day 9 72,872 vs 76,314 pg/mL, respectively). (2) ICAM-1 expression was significantly lower in preconditioned allografts (1.02 vs 2.01 mm(2)). (3) CD44 tissue levels were also found to be lower in preconditioned allografts (0.86 vs 1.13 mm(2)). (4) There was a significant relationship between tissue ICAM-1 expression and serum levels of soluble ICAM-1 (P < .02). CONCLUSIONS: IPc improves inflammatory indices in the early stages following intestinal transplantation, and this might lead to a preserved cellular, architectural, and functional graft status. Furthermore, our results support the use of soluble ICAM-1 as a marker of endothelial activation, and thence of inflammation and developing rejection.