Phytosterols in Lipid Emulsions Alter the Immune-Inflammatory Response in Neonatal Rats

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ESPR378
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Abstract: :

Background: Traditional lipid emulsions (LE) are derived from 100% soybean oil (SO) and contain high concentrations of ω6 fatty acids (FA) and plant cholesterols, known as phytosterols (PS). Fish-oil (FO) containing LE contain high concentrations ω3 FA and lower concentrations of PS. Animal and adult studies have consistently shown that FO containing LE provide therapeutic benefit via modulation of the immune-inflammatory response; whether this benefit is due to the altered FA profile, a decrease in PS concentration, or a combination thereof is currently unknown. To our knowledge, the independent effect of PS on the immune-inflammatory response has not been studied.


Objective: To determine the effect of PS exposure on plasma levels of immunologic factors including immunoglobulins, cytokines, and chemokines in neonatal rat pups.  


Methods: β-sitosterol, campesterol, and stigmasterol were dissolved in β-cyclodextrin (vehicle) to create a solution with a PS profile comparable to 20% Intralipid. Sprague-Dawley rat pups (n=5) received intraperitoneal injections of PS solution from P0-P14; a dosing regimen that approximates 2 g/kg/d Intralipid. Vehicle-injected pups (n=5) served as controls. Plasma IgG concentrations were quantified by ELISA. Twenty-two cytokines/chemokines were measured using ProcartaPlex multiplex bead-based immunoassays (ThermoFisher). The results were compared by Mann Whitney U test, and differences between groups were considered significant if p<0.05.


Results: Plasma PS concentrations were significantly elevated in pups receiving PS solution vs. vehicle (22.2 ± 0.7 vs. 13.8 ± 0.4 μg/mL, p=0.02) (Fig 1a) and comparable to PS levels found in preterm infants receiving Intralipid (Fig 1b). Plasma IgG concentrations were significantly decreased in PS exposed vs. vehicle exposed pups (1.8 ± 0.1 vs. 3.6 ± 0.4 mg/ml, p=0.008) (Fig 2a). An overall reduction in cytokine/chemokine levels in PS exposed pups was noted (Fig 2b).


Conclusions: This is the first study characterizing the independent effect of PS on the immune-inflammatory response in a neonatal animal model. Plasma IgG levels are halved in PS exposed animals, suggesting that short-term PS exposure contributes to a significant deficiency in humoral-mediated immunity. Given that up to 70% of the most vulnerable neonates admitted to the NICU receive parenteral nutrition, further mechanistic and clinical studies elucidating this immunological deficit are warranted.

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MidAtlantic Neonatology Associates; Goryeb Children's Hospital, Atlantic Health System
Goryeb Children's Hospital, Atlantic Health System
MidAtlantic Neonatology Associates
MidAtlantic Neonatology Associates
MidAtlantic Neonatology Associates

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