Immune function and leukocyte sequestration under the influence of parenteral lipid emulsions in healthy humans: a placebo-controlled crossover study.
BACKGROUND
It remains unclear whether immune modulation by lipids contributes to the high risk of infectious complications that is associated with the use of parenteral nutrition. Although mixed long- and medium-chain triacylglycerol (LCT-MCT)-containing emulsions, but not pure LCT emulsions, activate neutrophils and impair crucial leukocyte functions in vitro, in vivo studies have failed to corroborate these findings.


OBJECTIVE
The present investigation was conducted to evaluate the effects of LCT and LCT-MCT on immune function in healthy humans and to assess whether the lack of in vivo effects results from sampling errors due to extravascular sequestration of activated neutrophils.


METHODS
Saline, LCT-MCT, and LCT emulsions were administered intravenously for 4.5 h to 12 healthy volunteers in a randomized crossover design. Plasma triacylglycerol concentrations were clamped at a clinically relevant concentration of 3-5 mmol/L. Leukocyte population counts and neutrophil activation were assessed before and after infusion. Leukocyte sequestration was evaluated by monitoring the distribution of Technetium-99m-labeled autologous leukocytes during infusions.


RESULTS
Whereas LCT exerted no greater effects than did saline, LCT-MCT significantly decreased lymphocyte counts. However, no evidence for neutrophil activation was found with either lipid. Moreover, the clearance of radiolabeled leukocytes from the liver, spleen, and lungs was not altered by any lipid, which suggested that lipid emulsions do not induce leukocyte sequestration.


CONCLUSIONS
Short-term infusion of LCT-MCT (but not LCT) to healthy humans modulates leukocyte population counts but, in clear contrast with the in vitro situation, does not induce neutrophil activation. These disparate findings cannot be explained by MCT-induced leukocyte sequestration.
Versleijen
Michelle W
MW
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. m.versleijen@mdl.umcn.nl
Oyen
Wim J
WJ
Roelofs
Hennie M
HM
van Emst-de Vries
Sjenet E
SE
Willems
Peter H
PH
Jansen
Jan B
JB
Wanten
Geert J
GJ
D000328:Adult; D018592:Cross-Over Studies; D005217:Fat Emulsions, Intravenous / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology; D010289:Parenteral Nutrition, Total / Q000379:methods*; D019275:Radiopharmaceuticals / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology
D005217:Fat Emulsions, Intravenous; D019275:Radiopharmaceuticals; D017382:Reactive Oxygen Species; D014280:Triglycerides