Immunoregulation by Parenteral Lipids: Impact of the n‐3 to n‐6 Fatty Acid Ratio

BACKGROUND: The immune system is reported to be influenced by polyunsaturated fatty acids. Therefore, immunoregulation caused by intravenous fat emulsions with different n-3 to n-6 fatty acid ratios was studied in an in vivo model. METHODS: Experimental rat heart allotransplantation served as a defined immunologic challenge. Twenty percent emulsions of safflower oil (n-3 to n-6 = 1:370), fish oil (n-3 to n-6 = 7.6:1), and soybean oil (n-3 to n-6 = 1:6.5), and a 1:1 mixture of safflower oil and fish oil (n-3 to n-6 = 1:2.1) were continuously infused (9 g of fat per kg of body weight per day) after transplantation until complete rejection. The prolongation of graft survival, an accepted parameter of immunosuppression, was assessed. Beyond that, cytokine release by mitogen-stimulated peripheral-blood mononuclear cells (PBMCs) from animals exsanguinated on day 4 after transplantation was evaluated. RESULTS: The mean rejection time was 7.8 days in the sham-infused saline control group and 6.7 days in the safflower- and fish-oil-mixture group (oil control group). Continuous infusion of soybean oil prolonged the graft survival time to 10.4 days, fish oil to 12.3 days, and safflower oil to 13.3 days. PBMC alpha-tumor necrosis factor release was significantly reduced in the fish-oil group (51.9 +/- 13.0 pg/10(6) PBMCs vs 70.8 +/- 10.9 pg/10(6) PBMCs controls, p < .004). Interleukin-6 release was diminished in both the fish-oil group (22.2 +/- 13.6 pg/10(6) PBMCs vs 40.7 +/- 8.3 pg/10(6) PBMCs controls, p < .002) and the safflower-oil group (28.4 +/- 6.9 pg/10(6) PBMCs, p < .002). CONCLUSIONS: The n-3 to n-6 fatty acid ratio determined the immunoregulatory potential of intravenous fat emulsions in vivo. Both n-3 and n-6 fatty acids were immunosuppressive when applied as the main polyunsaturated fatty acid sources. PBMC cytokine release was significantly reduced in these groups. The more balanced the n-3 to n-6 ratios, the less immunosuppressive the fat emulsion. There was no immunosuppressive effect at an n-3 to n-6 ratio of 1:2.1.