Anti-inflammatory effects of ischemic preconditioning on small bowel allografts
Ricardo Camprodon Gazulla1, Matthew Bowles2, Javier de Oca Burguete3, Graham Pockley4
1Surgery, Chesterfield Royal Hospital, Chesterfield, United Kingdom; 2Surgery, Derriford Hospital, Plymouth, United Kingdom; 3Surgery, Hospital Universitari de Bellvitge, Barcelona, Spain; 4John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, United Kingdom
Introduction: Minimising the inflammatory events that follow transplantation may influence immediate graft function and improve outcome. Ischemic pre-conditioning (IPc) has been shown to ameliorate early inflammatory responses and it may also attenuate the potentially damaging inflammation after intestinal transplantation.
Aims:To determine the influence of graft 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 (HIT).
Methodology: Lewis rats received full-length pre-conditioned or non-pre-conditioned heterotopic Brown Norway intestinal allografts in the absence of immunosuppression. 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 sICAM-1 levels were determined using an R & D Systems Quantikine® enzyme immunoassay.
Results: (1) HIT led to a progressive increase in circulating levels of sICAM-1 in the post-transplantation period when compared to isografts (Day 3: 40479 vs. 42290 pg/ml; Day 5: 61593 vs. 36269 pg/ml; Day 7: 73309 vs. 37306 pg/ml; Day 9: 76314 vs. 42267 pg/ml, respectively). (2) IPc ameliorated serum levels of sICAM-1 until severe rejection (day 7) overcame this down-regulation (Day 3: 34304 vs. 40479 pg/ml; Day 5: 52441 vs. 61593 pg/ml; Day 7: 75114 vs. 73309 pg/ml; Day 9: 72872 vs. 64486 pg/ml,respectively). (3) Intra-graft ICAM-1 expression was significantly lower in IPc grafts (1.02 v 2.01 mm2). (4) CD44 tissue levels were also found to be lower in the IPc group (0.86 v 1.13 mm2).
Conclusions: IPc improves inflammatory indices in the early stages after ITx, which may have a role in maintaining graft integrity and barrier function. Further studies are required in order to determine whether IPc can improve long-term graft function and enhance survival in immunosuppressed recipients.