Immunomodulation by an Omega-6 Fatty Acid Reduced Mixed Lipid Emulsion in Murine Acute Respiratory Distress Syndrome.

Matthias Hecker,Natascha Sommer,Werner Seeger,Hartmut Dietrich,Martina B Schaefer,Konstantin Mayer,Matthias Rose,Andreas Hecker

doi:10.3390/jcm9072048

Abstract

Background: Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects of a modern, n-6-reduced lipid emulsion mixture in murine ARDS. Methods: Mice received an infusion of either normal saline solution, pure long-chain triglyceride (LCT) emulsion, or SMOF (soybean oil, medium-chain triglycerides, olive oil, and fish oil) before a lipopolysaccharide (LPS) challenge. Mice were sacrificed at different time points (0, 24, or 72 h) after ARDS induction, and an analysis of inflammatory cytokines, protein concentrations, and the cellular composition of the alveolar and interstitial compartments was performed with special focus on alveolar apoptosis and necrosis. Results: Mice infused with SMOF showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in alveolar spaces after LPS challenge compared to animals that received LCT. There were fewer cells in the lung interstitium of the SMOF group compared to the LCT group. Both lipid emulsions exerted pro-apoptotic and pro-necrotic properties on alveolar immune cells, with significantly increased necrosis in mice infused with LCT compared to SMOF. Conclusion: SMOF has both anti-inflammatory and pro-resolving influences in murine ARDS. Partial replacement of n-6 fatty acids with n-3/n-9 fatty acids may therefore benefit critically ill patients at risk for ARDS who require parenteral nutrition.

Highlights

Acute respiratory distress syndrome (ARDS) is a common disorder associated with high morbidity and mortality in intensive care units worldwide [1]
We investigated the impact of an n-6-reduced Lipid emulsions (LEs) mixture, SMOF, compared to a conventional, pure, long-chain triglyceride (LCT) emulsion in a murine model of ARDS
Protein leakage and the generation of pro-inflammatory cytokines were both lowered compared to animals infused with LCT

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a common disorder associated with high morbidity and mortality in intensive care units worldwide [1]. Lipid emulsions (LEs) are regarded as essential components of parenteral nutrition regimens applied clinically to critically ill patients [6]. In addition to providing adequate caloric support, both experimental and clinical studies have indicated that LEs might exert immunomodulatory properties [7,8,9] In this context, LEs have been shown to modify and influence cytokine release, leukocyte function, and the generation of lipid mediators which display both pro- and anti-inflammatory properties [10,11,12]. There were fewer cells in the lung interstitium of the SMOF group compared to the LCT group Both lipid emulsions exerted pro-apoptotic and pro-necrotic properties on alveolar immune cells, with significantly increased necrosis in mice infused with LCT compared to SMOF. Partial replacement of n-6 fatty acids with n-3/n-9 fatty acids may benefit critically ill patients at risk for ARDS who require parenteral nutrition

Methods

Results

Conclusion