Abstract

Background: Parenteral nutrition is often a mandatory therapeutic strategy for cases of septicemia. Likewise, therapeutic application of anti-oxidants, anti-inflammatory therapy, and endotoxin lowering, by removal or inactivation, might be beneficial to ameliorate the systemic inflammatory response during the acute phases of critical illness. Concerning anti-inflammatory properties in this setting, omega-3 fatty acids of marine origin have been frequently described. This study investigated the anti-inflammatory and LPS-inactivating properties of krill oil (KO)-in-water emulsion in human macrophages in vitro. Materials and Methods: Differentiated THP-1 macrophages were activated using specific ultrapure-LPS that binds only on the toll-like receptor 4 (TLR4) in order to determine the inhibitory properties of the KO emulsion on the LPS-binding capacity, and the subsequent release of TNF-α. Results: KO emulsion inhibited the macrophage binding of LPS to the TLR4 by 50% (at 12.5 µg/mL) and 75% (at 25 µg/mL), whereas, at 50 µg/mL, completely abolished the LPS binding. Moreover, KO (12.5 µg/mL, 25 µg/mL, or 50 µg/mL) also inhibited (30%, 40%, or 75%, respectively) the TNF-α release after activation with 0.01 µg/mL LPS in comparison with LPS treatment alone. Conclusion: KO emulsion influences the LPS-induced pro-inflammatory activation of macrophages, possibly due to inactivation of the LPS binding capacity.

Highlights

  • Sepsis and septic shock due to Gram-negative pathogens are responsible for significant morbidity and mortality in human populations [1]

  • Exogenous or endogenous stimulation of biological factors that modulate the extent of binding of LPS to monocytes and macrophages may play a pivotal role in determining the outcome of endotoxin exposure [1]

  • We used two binding assays to evaluate the interaction of LPS with macrophage-toll-like receptor 4 (TLR4) and the inhibitory effect of krill oil (KO)

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Summary

Introduction

Sepsis and septic shock due to Gram-negative pathogens are responsible for significant morbidity and mortality in human populations [1]. Exogenous or endogenous stimulation of biological factors that modulate the extent of binding of LPS to monocytes and macrophages may play a pivotal role in determining the outcome of endotoxin exposure [1]. In this context, serum factors that bind LPS may prevent macrophage activation [4]. This study investigated the anti-inflammatory and LPS-inactivating properties of krill oil (KO)-in-water emulsion in human macrophages in vitro. THP-1 macrophages were activated using specific ultrapure-LPS that binds only on the toll-like receptor 4 (TLR4) in order to determine the inhibitory properties of the KO emulsion on the LPS-binding capacity, and the subsequent release of TNF-α. Conclusion: KO emulsion influences the LPS-induced pro-inflammatory activation of macrophages, possibly due to inactivation of the LPS binding capacity

Methods
Results
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