Use of fish oil to prevent graft rejection.

Immunonutrition combining parenteral nutrition and pharmacological intervention has become of particular interest over the last few years. 12-3 Fatty acid-rich lipid emulsions have been developed for parenteral application in clinical situations, designed to shift the arachidonic acid (AA): eicosapentaenoic acid (EPA) value toward predominance of the latter lipid-mediator precursor. Many of the EPA-derived eicosanoids, i.e. 5-series cysteinyl leukotrienes (LT), LTBs and thromboxane (TX)A3, possess markedly reduced inflammatory and vasomotor potencies and even exert antagonistic effects to AA-derived lipid mediators (Leaf & Weber, 1988). Dietary supplementation with n-3 fatty acids has been shown to cut down on polymorphonuclear leucocyte (PMN)mediated and thrombocyte-related inflammatory events (Leaf & Weber, 1988) and to reduce proinflammatory cytokine synthesis in mononuclear cells (Endres et al. 1989). Based on the properties mentioned previously, n-3 fatty acids might even have advantageous effects on the acute rejection process after allotransplantation, in which inflammatory and specific immunological reactions are involved. Both experimental and clinical studies have recently shown that n-3 fatty acid-enriched diets reduce nephrotoxicity and graft rejection in cyclosporine A-treated recipients (Kelley et al. 1990; van der Heide et al. 1993). Since dietary supplementation with EPA is associated with slow kinetics and limited availability for inflammatory processes, the intravenous route of n-3 lipid administration might prove superior in an immunological reaction as grave as acute rejection. In the present study, a fish oil-based lipid emulsion was continuously infused after heterotopic rat heart allotransplantation to assess the impact on graft rejection, with particular focus on inflammatory and specific immunological processes. Graft survival, mobilization of immunocompetent cells, cytokine release by mononuclear cells, plasma fatty acid profiles and lipid mediator generation were evaluated and compared with data derived from the infusion of a soyabean oil-based lipid preparation.