Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4

• Published in: Toxicology in vitro 2015-10, Vol.29 (7), p.1851-1858
• Main Authors: Olthof, Evelyn D., Gülich, Alexandra F., Renne, Mike F., Landman, Sija, Joosten, Leo A.B., Roelofs, Hennie M.J., Wanten, Geert J.A.
• Format: Article
• Language: English
• Subjects: Emulsions; Fatty Acids, Omega-3 - pharmacology; Fish oil; Humans; Immune system; Leukocytes - drug effects; Leukocytes - metabolism; Medium chain triglyceride; Micelles; Parenteral nutrition; Reactive Oxygen Species - metabolism; Toll like receptor 4; Toll-Like Receptor 4 - metabolism; Triglycerides - pharmacology
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2015.07.004

•Parenteral lipids modulate immune function depending on the fatty acid composition.•Parenteral medium chain triglycerides activate the immune system in vitro.•Leukocyte activation by medium chain triglycerides does not involve TLR-4 signaling.•Medium chain triglycerides induced immune activation is not modulated by fish oil. Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO. To test this hypothesis we assessed effects of addition of various commercially available mixed parenteral lipid emulsions, n-3 FA and of TLR-4 inhibition on MCT-induced human immune cell activation by evaluation of the expression of leukocyte membrane activation markers and reactive oxygen species (ROS) production. All MCT-containing lipid emulsions activated leukocytes by inducing changes in expression of membrane markers and stimulus induced ROS production, whereas MCT-free lipid emulsions lacked this effect. Moreover, addition of n-3 FA to LCT/MCT did not prevent MCT-induced immune activation. TLR-4 inhibitors did not distinctly modulate MCT-induced changes in immune function. Taken together, these findings suggest that leukocyte activation by parenteral MCTs does not involve TLR-4 signaling and is not modulated by n-3 FA in FO-, but is exerted via different signaling pathways.