Immunosuppression by parenteral lipid emulsions in a model of defined immunostimulation

The immunosuppressive effect of intravenous fat emulsions with different n-3/n-6 fatty acid ratio was studied in the heterotopic rat heart allotransplant model. Twenty percent emulsions of safflower oil (n-3/n-6 = 1/370), fish oil (7.6/1), soybean oil (1/6.5) and a 1:1 mixture of safflower and fish oil (1/2, 1; oil control group) were continuously infused (9 g fat/Kg b.w./day; n = 10 each group) after transplantation until rejection. Graft survival time, subpopulations of infiltrating and circulating immunocompetent cells and Interleukin-6 release of circulating monocytes were analyzed. In the safflower oil, fish oil and soybean oil groups graft survival was prolonged to 13.3, 12.3 and 10.4 days vs. 6.7 days in the oil control group and 7.8 days in the saline control group (p < 0.01). In the two groups with the highest prolongation of graft survival the number of infiltrating cells was reduced by up to 50 percent and the peripheral blood monocyte interleukin-6 release by up to 45 percent. Beyond that, circulating T-cells were reduced in the fish oil group. Intravenous fat emulsions show a varying immunomodulatory effect in dependence of the n-3/n-6 fatty acid ratio. Both n-6 and n-3 fatty acids, if applied as main fatty acid source, exert immunosuppressive effects by a diminished infiltration, mobilisation and cytokine release of immunocompetent cells. Soybean oil with a more balanced n-3/n-6 fatty acid ratio than safflower is significantly less immunosuppressive than safflower oil and fat emulsions with a n-3/n-6 fatty acid ratio of 1/2 are immunologically neutral.