NUTRITIONAL IMMUNOMODULATION ENHANCES CARDIAC ALLOGRAFT SURVIVAL IN RATS TREATED WITH DONOR-SPECIFIC TRANSFUSION AND CYCLOSPORINE

Abstract

The aim of this study was to assess the efficacy of an enteral diet fortified with arginine, RNA, and fish oil (Impact), alone and in combination with cyclosporine (CsA) and donor-specific transfusion (DST) on allograft survival in the ACI:Lewis rat cardiac transplant model. Animals were fed ad libitum with either standard rat chow or Impact diet. Six groups were studied; these consisted of untreated recipients fed either standard diet or Impact diet; recipients treated with CsA 10 mg/kg on the day prior to engraftment (day-1) followed by 2.5 mg/kg/d, day 0-->day+13 and fed with either standard diet or Impact; and animals given a DST (1 ml) on day-1, CsA as described previously and fed either standard diet or Impact. Untreated animals standard diet (group 1, n = 8) rejected their allografts at 7.0 +/- 0.0 days, while those fed Impact (group 2, n = 9) had graft survival of 12.8 +/- 2.1 days, (P = .01 versus group 1). Animals treated with CsA alone and standard diet (group 3, n = 9) rejected at 30.3 +/- 4.8 days, while the combination of CsA and Impact diet (group 4, n = 8) rejected at 33.0 +/- 9.5 days--minimally improved survival compared with group 3. Animals treated with DST/CsA and standard diet (group 5, n = 7) rejected at 72.1 +/- 6.8 days, while the substitution of Impact for standard diet (group 6, n = 8) led to a significant graft prolongation to 275 +/- 53 days, n = 8 (P < .015 vs. groups 1-5). These data suggest that Impact diet alone can have potent immunomodulatory properties but may require the addition of DST/CsA to realize its potential. These findings underscore the potential of dietary immunomodulatory therapy to prevent rejection and promote tolerance to solid organ allografts.