Impact of omega-3 fatty acid enriched TPN on leukotriene synthesis by leukocytes after major surgery

Major surgery leads to post-traumatic immune dysregulation which is driven by the activation of potent proinflammatory mediators including the leukotrienes (LTs). The LTs of the four-series derive from arachidonic acid (an omega-6 fatty acid). In contrast, LTs of the five-series are metabolic products of eicosapentaenoic acid (an omega-3 fatty acid) and exert less biological activities. Therapeutical strategies to attenuate proinflammatory signals include the provision of omega-3 fatty acids. Thirty patients with major elective abdominal surgery and an indication for total parenteral nutrition (TPN) were compared in a prospective, double blind, randomized study of two parallel groups. Group 1 (n=14) received an omega-3 fatty acid enriched 20% lipid emulsion (MCT:LCT:fish OIL = 5:4:1, MLF541; Lipoplus®) for 5 days postoperatively. Group 2 (n=16) received a standard 20% fat emulsion (LCT; Intralipid®). The LT release from whole blood leukocytes stimulated with Ca-ionophore was analyzed preoperatively and on postoperative days 1, 6 and 8 by HPLC. There was a significant increase in the generation of LTB5 (P=0.0035) and in the ratio of LTB5/LTB4 (P=0.0017) the omega-3 group, but not in the reference group after 5 days infusion of the lipid emulsions. The omega-6/omega-3 fatty acid ratio 3:1 of the newly developed MLF541 lipid emulsion is appropriate to increase the synthesis of the biologically less active leukotrienes of the five-series. Nutritive enrichment with omega-3 fatty acids in a balanced ratio with omega-6 fatty acids is an important step to avoid hyperinflammatory situations in patients after major surgery.