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

Evelyn D Olthof; Alexandra F Gülich; Mike F Renne; Sija Landman; Leo A B Joosten; Hennie M J Roelofs; Geert J A Wanten

doi:10.1016/j.tiv.2015.07.004

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

Evelyn D Olthof, Alexandra F Gülich, Mike F Renne, Sija Landman, Leo A B Joosten, Hennie M J Roelofs, Geert J A Wanten

Radboud University Medical Center

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Original language	English
Pages (from-to)	1851-8
Number of pages	8
Journal	Toxicology in Vitro
Volume	29
Issue number	7
DOIs	https://doi.org/10.1016/j.tiv.2015.07.004
Publication status	Published - 7 Jul 2015

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10.1016/j.tiv.2015.07.004

1-s2.0-S0887233315001654-mainFinal published version, 393 KBLicence: Taverne

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@article{f9ccf373755e4a3882fb42b58c394a48,

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

abstract = "BACKGROUND: 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.MATERIALS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.",

author = "Olthof, {Evelyn D} and G{\"u}lich, {Alexandra F} and Renne, {Mike F} and Sija Landman and Joosten, {Leo A B} and Roelofs, {Hennie M J} and Wanten, {Geert J A}",

year = "2015",

month = jul,

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doi = "10.1016/j.tiv.2015.07.004",

language = "English",

volume = "29",

pages = "1851--8",

journal = "Toxicology in Vitro",

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TY - JOUR

T1 - Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4

AU - Olthof, Evelyn D

AU - Gülich, Alexandra F

AU - Renne, Mike F

AU - Landman, Sija

AU - Joosten, Leo A B

AU - Roelofs, Hennie M J

AU - Wanten, Geert J A

PY - 2015/7/7

Y1 - 2015/7/7

N2 - BACKGROUND: 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.MATERIALS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.

AB - BACKGROUND: 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.MATERIALS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.

U2 - 10.1016/j.tiv.2015.07.004

DO - 10.1016/j.tiv.2015.07.004

M3 - Article

C2 - 26162596

SN - 0887-2333

VL - 29

SP - 1851

EP - 1858

JO - Toxicology in Vitro

JF - Toxicology in Vitro

IS - 7

ER -

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

Abstract

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