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 polyunsa turated 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 allotransplantat ion served as a defined immunologic challenge. Twenty percent emulsion s 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 comp lete rejection. The prolongation of graft survival, an accepted parame ter 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. Re sults: 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 gro up (oil control group). Continuous infusion of soybean oil prolonged t he graft survival time to 10.4 days, fish oil to 12.3 days, and safflo wer oil to 13.3 days. PBMC alpha-tumor necrosis factor release was sig nificantly 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 us 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). Conclusio ns: The n-3 to n-6 fatty acid ratio determined the immunoregulately po tential of intravenous fat emulsions in vivo. Both n-3 and n-6 fatty a cids were immunosuppressive when applied as the main polyunsaturated f atty acid sources. PBMC cytokine release was significantly reduced in these groups. The more balanced the n-3 to n-6 ratios, the less immuno suppressive the fat emulsion. There was no immunosuppressive effect at an n-3 to n-6 ratio of 1:2.1.