Immunomodulation by fish-oil containing lipid emulsions in murine acute respiratory distress syndrome

Hecker, Matthias; Ott, Juliane; Sondermann, Christoph; Schaefer, Martina Barbara; Obert, Martin; Hecker, Andreas; Morty, Rory E.; Vadász, István; Herold, Susanne; Rosengarten, Bernhard; Witzenrath, Martin; Seeger, Werner; Mayer, Konstantin

doi:10.1186/cc13850

Cited by 26 publications

(22 citation statements)

References 40 publications

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“…Supporting our findings, FO emulsion preconditioning for 3 days was previously found to significantly lower the serum and lung levels of TNF-α, IL-1β and IL-6 in an ischemia-reperfusion ALI model in rats [29]. Clinoleic or Omegaven preconditioning also reduced TNF-α in BALF in the present study, similar to previous findings from humans [7], rats [19,29] and mice [30,31], indicating that infusion of FO achieved a significant reduction of TNF-α upon ALI induction.…”

Section: Discussionsupporting

confidence: 92%

“…To minimize the number of animals, only one dose of lipid emulsion for preconditioning, LPS for challenge, a single timepoint for ending the experiment, all based on literature research. The emulsion doses were comparable to those (1.5 g/kg/d) used in reference [31]. Since no mechanical ventilation machine was available for experimental animals, a reasonable timepoint (8 h after LPS treatment) was chosen to ensure the survival of the challenged rats.…”

Section: Discussionmentioning

confidence: 99%

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Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver

Huang

et al. 2020

Lipids Health Dis

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Background: Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. We sought to study whether preconditioning with representative of lipid emulsions for one week could benefit rats from ALI. Methods: Using a lipopolysaccharide (LPS)-induced ALI rat model and techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Results: PGE 2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE 2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB 4 than the LPS, Clinoleic, or Omegaven group. In contrast to Intralipid, rats pretreated with Clinoleic or Omegaven significantly decreased their production of inflammatory mediators (IL-1 β, IL-6 and TNF-α), had less apoptosis in the lung tissues, and Omegaven greatly improved liver function upon lipopolysaccharide (LPS) challenge. Conclusions: In an ALI setting, preconditioning with Omegaven or Clinoleic was better than Intralipid in decreasing the intensity of the cytokine storm and apoptosis caused by LPS challenge, and Omegaven in addition had the potential to improve liver function. The results from the present study set a basis for further investigation of the molecular mechanisms of ALI, including the up-and downstream pathways of proinflammatory factor production, in search of (small) molecules intervening with the pathogenesis of ALI in order to translate relevant research findings into clinical benefit for patients with ALI. The use of Omegaven or Clinoleic, particularly in patients with ALI, is still characterized by uncertainty due to a lack of relevant studies. Future investigations must specifically focus on the route of administration and mode of application (enteral vs. parenteral/bolus vs. continuous), determining an optimal dose of Omegaven or Clinoleic, and the defining the best timepoint(s) for administration. Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. The effect of lipid emulsion via parenteral nutrition on liver function was first time evaluated in rats in an ALI setting. The comparison of three forms of lipid emulsion in a rat model of acute lung injury was first time studied. The fish oilbased lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver

Huang

et al. 2020

Lipids Health Dis

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“…This is consistent with a previous study, which showed that n -3 PUFAs increased the levels of IL-10 in mice subjected to Citrobacter rodentium infection [27]. Increased levels of anti-inflammatory cytokines confirmed that n -3 PUFAs could alleviate the systemic inflammatory response induced by injury [28,29,30]. Furthermore, based on previous studies, n -3 PUFAs may also reverse the downregulation of lysozyme and mucin 2 after HSR [21,31,32].…”

Section: Discussionsupporting

confidence: 92%

Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation

et al. 2016

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n-3 polyunsaturated fatty acids (PUFAs) can improve the function of the intestinal barrier after damage from ischemia-reperfusion or hemorrhagic shock resuscitation (HSR). However, the effects of n-3 PUFAs on intestinal microbiota and the innate immunity of the intestinal mucosa after HSR remain unclear. In the present study, 40 C57BL/6J mice were randomly assigned to five groups: control, sham, HSR, HSR + n-3 PUFAs and HSR + n-6 PUFAs. Mice were sacrificed 12 h after HSR. Liver, spleen, mesenteric lymph nodes and terminal ileal tissues were collected. Intestinal mucosae were scraped aseptically. Compared with the HSR group, the number of goblet cells increased, expression of mucin 2 was restored and disturbed intestinal microbiota were partly stabilized in the PUFA-administered groups, indicating that both n-3 and n-6 PUFAs reduced overproliferation of Gammaproteobacteria while promoting the growth of Bacteroidetes. Notably, n-3 PUFAs had an advantage over n-6 PUFAs in improving ileal tissue levels of lysozyme after HSR. Thus, PUFAs, especially n-3 PUFAs, partly improved the innate immunity of intestinal mucosa in mice after HSR. These findings suggest a clinical rationale for providing n-3 PUFAs to patients recovering from ischemia-reperfusion.

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“…prostaglandins, leukotrienes) (Calder, 2015;Hecker et al, 2015b;Mayer and Seeger, 2010). Special focus is placed on the supplementation of omega-3 (n-3)-derived lipid emulsions containing fish oil (FO) with a high content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which were displayed in both experimental and clinical studies and which are considered rather controversial results (Hecker et al, 2014a;Manzanares et al, 2014;Mayer and Seeger, 2010;Wanten, 2015). The recent identification of resolvins as a novel promising class of n-3 derived lipid mediators is in this context of particular interest because they displayed beneficial effects concerning resolution of inflammation in several disease models (Arita et al, 2005a;Uddin and Levy, 2011).…”

Section: Introductionmentioning

confidence: 99%

Resolvin E1 Improves Mitochondrial Function in Human Alveolar Epithelial Cells during Severe Inflammation

Mayer

Sommer

Hache

et al. 2019

Lipids

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Severe inflammatory disorders such as sepsis are a major cause of morbidity and mortality worldwide. Mitochondrial dysfunction is regarded as a key feature involved in inflammation pathogenesis. In the present study, we investigated the impact of the omega‐3 fatty acid‐derived lipid mediator Resolvin E1 (RvE1) on mitochondrial function in experimental pulmonary inflammation. RvE1 was found to exert anti‐inflammatory properties in human alveolar epithelial cells during severe inflammation. RvE1 is capable of restoring inflammation‐induced mitochondrial dysfunction and the impaired imbalance of mitochondrial fission and fusion. Experimental inhibition of mitochondrial fission with Mdivi‐1 in our model is associated with a significantly reduced inflammatory response and improved mitochondrial function. These findings suggest a novel functional mechanism for the beneficial effects of RvE1 in experimental pulmonary inflammatory reactions.

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Immunomodulation by fish-oil containing lipid emulsions in murine acute respiratory distress syndrome

Cited by 26 publications

References 40 publications

Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver

Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver

Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation

Resolvin E1 Improves Mitochondrial Function in Human Alveolar Epithelial Cells during Severe Inflammation

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