Parenteral Nutrition with Fish Oil Modulates Cytokine Response in Patients with Sepsis

Abstract

Infusion of fish oil-based (n-3) lipids may influence leukocyte function and plasma lipids in critical care patients. Twenty-one patients with sepsis requiring parenteral nutrition were randomized to receive an n-3 lipid emulsion rich in eicosapentaenoic acid and docosahexaenoic acid or a conventional (n-6) lipid emulsion (index fatty acid: arachidonic acid) for 5 days. The impact on plasma-free fatty acids, mononuclear leukocyte cytokine generation, and membrane fatty acid composition was examined. Cytokine synthesis by isolated mononuclear leukocyte was elicited by endotoxin. Before the onset of lipid infusion therapy, plasma-free fatty acid concentrations were greatly increased in septic patients, with arachidonic acid by far surpassing eicosapentaenoic acid and docosahexaenoic acid, a feature maintained during conventional lipid infusion. Within 2 days of fish oil infusion, free n-3 fatty acids increased, and the n-3/n-6 ratio was reversed, with rapid incorporation of n-3 fatty acids into mononuclear leukocyte membranes. Generation of proinflammatory cytokines by mononuclear leukocytes was markedly amplified during n-6 and was suppressed during n-3 lipid application. After termination of lipid administration, free n-3 fatty acid concentrations and mononuclear leukocyte cytokine synthesis returned to preinfusion values. Use of lipid infusions might allow us to combine intravenous alimentation with differential impact on inflammatory events and immunologic functions in patients with sepsis.

Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers

“…7 ln critically ill humans with severe sepsis, intravenous FO reduced ex vivo cytokine release by monocytes in response to LPS. 37 Surprisingly, although we observed a marked increase in IL-6 and TNF-a in our subjects, cytokine release was not significantly influenced by FO supplementation suggesting that FO did not act primarily by down regulating cytokines release. Similar observation was reported in healthy humans after an intramuscular injection of typhoid vaccine: prior supplementation with FO failed to blunt the response of TNF-a (although, in contrast to our present observation, it significantly reduced IL 1 and IL6 concentrations).…”

Rationale and use of n-3 fatty acids in artificial nutrition

“…Production of TNFa, IL-1b, IL-6, IL-8 and IL-10 by endotoxin-stimulated mononuclear cells did not increase during infusion of the fish oil-containing emulsion, whereas production of the four pro-inflammatory cytokines was markedly elevated during the first 2 d of soyabean oil infusion (74) . These studies establish that infusion of long-chain n-3 PUFA into patients with sepsis can modulate inflammatory mediator production and related inflammatory processes.…”

Polyunsaturated Fatty Acids, Ulcerative Colitis and Cancer Prevention

“…Several studies have shown the mechanisms by which genes may influence the metabolism of nutrients, as well as the mechanisms by which nutrients can influence gene expression (Simopoulos et al 2008, Paolini-Giacobini et al 2003, Calder 2007. With advances in science, and emphasis on the study of nutrigenomics and nutrigenetics, it has been shown that certain nutrients can influence the inflammatory response, accelerating or regressing the development of many diseases (Heller et al 2002, Weiss et al 2002, Mayer et al 2003, Paolini-Giacobini et al 2003, Simopoulos et al 2008. Stern et al (2009), from the Singapore Chinese Health Study, through analyses taking into account variants in genes that are relevant for the proposed PUFAs mechanism of actionhypothesised that the genes which play key roles in the pathways that repair PUFA-induced damage might modify the effect of these FA on colorectal cancer.…”