Immunosuppression by n-3 fatty acids comparison of glycerol vs. ethyl esters

Abstract

Intravenous fish oil prolongs graft survival in a heterotopic cardiac transplant model (PVG rats (RT 1 c) × Wistar/Kyoto rats (RT 1 1)). This study elaborates the impact of the ester group on the immunosuppressive potential of n-3 fatty acids. Twenty per cent fish oil emulsions (glycerol esters, ethyl esters or concentrated ethyl esters; 9g fat/kg body weight/d) were given by continuous intravenous infusion after transplantation until complete rejection. Fish oil glycerol esters prolonged the heart graft survival time to 12.5 vs. 9.5 d (control group infused with a corresponding amount of soybean oil) (p<0.005, Mantel-Haenszel χ-square test). No prolongation of graft survival was achieved by infusing fish oil ethyl esters or concentrated ethyl esters (9.0 or 9.1 d, respectively). In the fish oil glycerol ester group all subpopulations of graft infiltrating cells were up to 50 percent lower than in the control group, while there was no significant difference in the two ethyl ester groups. PBMC Interleukin(IL)-6 release was significantly reduced in the fish oil glycerol ester group ( 22.1±4.2 pg 10 6 PBMC ) compared to the controls ( 73±2.6 pg 10 6 PBMC , p<0.0001, Student's t-test), but not in the ethyl ester groups ( 98.2±5.0 pg 10 6 PBMC and 88.0±6.2 pg 10 6 PBMC , resp.). Our data demonstrate that parenteral n-3 fatty acids prolong acute rejection and inhibit PBMC IL-6 release, activation and infiltration of specific immunocompetent cells only as glycerol esters, but not as ethyl esters.