Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses in Preterm Pigs

Abstract

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1 ± 0.0 to 9.7 ± 1.9, p < 0.001), docosahexaenoic acid, DHA (day 0 = 2.5 ± 0.7 to 13.6 ± 2.9, p < 0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1β increased at the first hour of LPS infusion (296.6 ± 308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p < 0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit the initial LPS-induced inflammatory responses in preterm pigs.

Lipid Metabolism in Inflammation and Immune Function

“…While many studies investigating the role of lipids in regulating immune function and inflammation target acute and chronic diseases in adults, two studies within this Special Issue highlight the important biological roles of lipids in early life. Accordingly, Yakah et al [ 5 ] and Hellström et al [ 6 ] investigated the association between fatty acid profiles and inflammatory markers in preterm animal models and infants, respectively, and provide evidence that underscores the importance of balancing AA:DHA ratios to optimize health outcomes in infancy.…”

“…In their original research article, Yakah et al [ 5 ] investigated the effects of administering different lipid emulsions on inflammatory immune responses to Escherichia coli -derived LPS in preterm piglets, which possess similar degrees of development and clinical profiles to human infants at 32 weeks gestation and greater. This research has important clinical implications, given that lipid emulsions that are rich in either soybean oil or n-3 polyunsaturated fatty acids are commonly prescribed to preterm infants, yet are associated with different health outcomes.…”

Effect of Immune Stress on Growth Performance and Immune Functions of Livestock: Mechanisms and Prevention

“…n3 FA can also reduce the expression of PGE2 and the level of inflammatory cytokines in the serum induced by LPS [ 131 ]. Fish oil can reduce the release of inflammatory cytokines and improve the growth performance in IS pigs [ 47 , 132 ]. While adding fish oil to the diet can increase cellular immunity and reduce the inflammation index in animals exposed to IS [ 133 ], increasing the ratio of n3 to n6 fatty acids in the diet can inhibit the inflammatory response, thereby improving the animals’ performance [ 134 ].…”