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Anti-inflammatory and anti-fibrotic profile of fish oil emulsions used in parenteral nutrition-associated liver disease.

Pastor-Clerigues A, Marti-Bonmati E, Milara J, Almudever P, Cortijo J - PLoS ONE (2014)

Bottom Line: However, its clinical effectiveness in adults has been scarcely reported.The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced.Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD.

View Article: PubMed Central - PubMed

Affiliation: Hospital Pharmacy, Clinical Nutrition Unit, University General Hospital Consortium, Valencia, Spain.

ABSTRACT
Home parenteral nutrition (PN) is associated with many complications including severe hepatobiliary dysfunction. Commercial ω-6 fatty acid-soybean based-lipid emulsions in PN may mediate long term PN associate liver disease (PNALD) whereas ω-3-fish oil parenteral emulsions have shown to reverse PNALD in children. However, its clinical effectiveness in adults has been scarcely reported. In this work, we study the role of soybean and fish oil lipid commercial emulsions on inflammatory and profibrotic liver markers in adults with long term PNALD and in in vitro cellular models. Inflammatory and profibrotic markers were measured in serum of ten adults with long term PNALD and in culture supernatants of monocytes. Liver epithelial to mesenchymal transition (EMT) was induced by transforming growth factor beta 1 (TGFβ1) to evaluate in vitro liver fibrosis. Omegaven®, a 100% fish oil commercial emulsion, was infused during four months in two patients with severe long term PNALD reversing, at the first month, the inflammatory, profibrotic and clinical parameters of PNALD. The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced. The other patients under chronic soybean oil-based PN showed elevated inflammatory and profibrotic parameters. In vitro human monocytes stimulated with lipopolysaccharide induced a strong inflammatory response that was suppressed by Omegaven®, but increased by soybean emulsions. In other experiments, TGFβ1 induced EMT that was suppressed by Omegaven® and enhanced by soybean oil lipid emulsions. Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD.

No MeSH data available.


Related in: MedlinePlus

Effect of different commercial parenteral lipid emulsions on Lipopolysaccharide (LPS)-induced IL-2 and IL-12 secretion in human monocytes.Human monocytes were isolated from healthy subjects and incubated in presence or absence of lipid emulsions Omegaven® 10%, Lipofundin MCT/LCT® 20%, ClinOleic® 20% or SMOFlipid® 20% at different dilutions, for 30 min followed by LPS 1 µg/mL stimulation for additional 24 hours. (A) IL-2 and (B) IL-12 were measured in cell culture supernatants. The effect of lipid emulsions without stimulus was tested at 1/10 dilution. Results are expressed as means ± SEM of six independent experiments. One-way ANOVA was followed by the post hoc Bonferroni test. *p<0.05 related to the control group. #p<0.05 values below stimulus; ⊥p<0.05 values above the stimulus.
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pone-0115404-g007: Effect of different commercial parenteral lipid emulsions on Lipopolysaccharide (LPS)-induced IL-2 and IL-12 secretion in human monocytes.Human monocytes were isolated from healthy subjects and incubated in presence or absence of lipid emulsions Omegaven® 10%, Lipofundin MCT/LCT® 20%, ClinOleic® 20% or SMOFlipid® 20% at different dilutions, for 30 min followed by LPS 1 µg/mL stimulation for additional 24 hours. (A) IL-2 and (B) IL-12 were measured in cell culture supernatants. The effect of lipid emulsions without stimulus was tested at 1/10 dilution. Results are expressed as means ± SEM of six independent experiments. One-way ANOVA was followed by the post hoc Bonferroni test. *p<0.05 related to the control group. #p<0.05 values below stimulus; ⊥p<0.05 values above the stimulus.

Mentions: Omegaven® (1/10-1/1000) dose-dependently inhibited the LPS-induced TGFβ1 and MMP-9 release (Figs. 2A and 2B) and decreased basal TGFβ1 and MMP-9 secretion in human monocytes. Conversely, Lipofundin MCT/LCT® (1/10-1/1000) dose-dependently increased TGFβ1 and MMP-9 secretion induced by LPS and increased the basal release per se (Figs. 2A and 2B). SMOFlipid® slightly reduced TGFβ1 secretion at 1/10 dilution whereas ClinOleic® lipid emulsion attenuated only MMP-9 release at 1/10 concentration (Figs. 2A and 2B). In other experiments, Omegaven® (1/10-1/1000) dose-dependently inhibited the release of the pro-inflammatory cytokines IL-6, TNFα (Figs. 3A and 3B), IL-8, IL-1β (Fig. 4) as well as the TH2 cytokines GM-CSF, IL-5 and IL-4 (Figs. 5 and 6) induced by LPS. Lipofundin MCT/LCT® (1/10-1/1000) showed a pro-inflammatory profile elevating even more the LPS-induced IL-8, IL-1β (Fig. 4A and 4B), GM-CSF (Fig. 5A) and IL-4 (Fig. 6A) without affecting IL-6 or TNFα (Fig. 3A and 3B). Furthermore, cell exposure to Lipofundin MCT/LCT® (1/10) without stimulus also showed a pro-inflammatory profile, increasing significantly TNFα, IL-8 and GM-CSF release. ClinOleic® (1/10-1/1000) did not modify the increase of pro-inflammatory cytokines, with the exception of a small increase of IL-1β, GM-CSF and IL-4. SMOFlipid® (1/10-1/1000) showed a variable profile, increasing the LPS-induced IL-8 and GM-CSF release and inhibiting the secretion of IL-1β and IL-4. Finally, the stimulation of monocytes with LPS increased the release of TH1 cytokines IL-10 and IL-2 while downregulated the secretion of IL-12. Omegaven® (1/10-1/1000) suppressed the IL-10 and IL-2 release and increased IL-12 to control levels (Fig. 6 and 7). Lipofundin MCT/LCT®, SMOFlipid® and ClinOleic® dose-dependently inhibited the increase of IL-10 and IL-2 release induced by LPS, and only ClinOleic® at 1/10 concentration elevated IL-12 to control levels (Figs. 6 and 7).


Anti-inflammatory and anti-fibrotic profile of fish oil emulsions used in parenteral nutrition-associated liver disease.

Pastor-Clerigues A, Marti-Bonmati E, Milara J, Almudever P, Cortijo J - PLoS ONE (2014)

Effect of different commercial parenteral lipid emulsions on Lipopolysaccharide (LPS)-induced IL-2 and IL-12 secretion in human monocytes.Human monocytes were isolated from healthy subjects and incubated in presence or absence of lipid emulsions Omegaven® 10%, Lipofundin MCT/LCT® 20%, ClinOleic® 20% or SMOFlipid® 20% at different dilutions, for 30 min followed by LPS 1 µg/mL stimulation for additional 24 hours. (A) IL-2 and (B) IL-12 were measured in cell culture supernatants. The effect of lipid emulsions without stimulus was tested at 1/10 dilution. Results are expressed as means ± SEM of six independent experiments. One-way ANOVA was followed by the post hoc Bonferroni test. *p<0.05 related to the control group. #p<0.05 values below stimulus; ⊥p<0.05 values above the stimulus.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264955&req=5

pone-0115404-g007: Effect of different commercial parenteral lipid emulsions on Lipopolysaccharide (LPS)-induced IL-2 and IL-12 secretion in human monocytes.Human monocytes were isolated from healthy subjects and incubated in presence or absence of lipid emulsions Omegaven® 10%, Lipofundin MCT/LCT® 20%, ClinOleic® 20% or SMOFlipid® 20% at different dilutions, for 30 min followed by LPS 1 µg/mL stimulation for additional 24 hours. (A) IL-2 and (B) IL-12 were measured in cell culture supernatants. The effect of lipid emulsions without stimulus was tested at 1/10 dilution. Results are expressed as means ± SEM of six independent experiments. One-way ANOVA was followed by the post hoc Bonferroni test. *p<0.05 related to the control group. #p<0.05 values below stimulus; ⊥p<0.05 values above the stimulus.
Mentions: Omegaven® (1/10-1/1000) dose-dependently inhibited the LPS-induced TGFβ1 and MMP-9 release (Figs. 2A and 2B) and decreased basal TGFβ1 and MMP-9 secretion in human monocytes. Conversely, Lipofundin MCT/LCT® (1/10-1/1000) dose-dependently increased TGFβ1 and MMP-9 secretion induced by LPS and increased the basal release per se (Figs. 2A and 2B). SMOFlipid® slightly reduced TGFβ1 secretion at 1/10 dilution whereas ClinOleic® lipid emulsion attenuated only MMP-9 release at 1/10 concentration (Figs. 2A and 2B). In other experiments, Omegaven® (1/10-1/1000) dose-dependently inhibited the release of the pro-inflammatory cytokines IL-6, TNFα (Figs. 3A and 3B), IL-8, IL-1β (Fig. 4) as well as the TH2 cytokines GM-CSF, IL-5 and IL-4 (Figs. 5 and 6) induced by LPS. Lipofundin MCT/LCT® (1/10-1/1000) showed a pro-inflammatory profile elevating even more the LPS-induced IL-8, IL-1β (Fig. 4A and 4B), GM-CSF (Fig. 5A) and IL-4 (Fig. 6A) without affecting IL-6 or TNFα (Fig. 3A and 3B). Furthermore, cell exposure to Lipofundin MCT/LCT® (1/10) without stimulus also showed a pro-inflammatory profile, increasing significantly TNFα, IL-8 and GM-CSF release. ClinOleic® (1/10-1/1000) did not modify the increase of pro-inflammatory cytokines, with the exception of a small increase of IL-1β, GM-CSF and IL-4. SMOFlipid® (1/10-1/1000) showed a variable profile, increasing the LPS-induced IL-8 and GM-CSF release and inhibiting the secretion of IL-1β and IL-4. Finally, the stimulation of monocytes with LPS increased the release of TH1 cytokines IL-10 and IL-2 while downregulated the secretion of IL-12. Omegaven® (1/10-1/1000) suppressed the IL-10 and IL-2 release and increased IL-12 to control levels (Fig. 6 and 7). Lipofundin MCT/LCT®, SMOFlipid® and ClinOleic® dose-dependently inhibited the increase of IL-10 and IL-2 release induced by LPS, and only ClinOleic® at 1/10 concentration elevated IL-12 to control levels (Figs. 6 and 7).

Bottom Line: However, its clinical effectiveness in adults has been scarcely reported.The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced.Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD.

View Article: PubMed Central - PubMed

Affiliation: Hospital Pharmacy, Clinical Nutrition Unit, University General Hospital Consortium, Valencia, Spain.

ABSTRACT
Home parenteral nutrition (PN) is associated with many complications including severe hepatobiliary dysfunction. Commercial ω-6 fatty acid-soybean based-lipid emulsions in PN may mediate long term PN associate liver disease (PNALD) whereas ω-3-fish oil parenteral emulsions have shown to reverse PNALD in children. However, its clinical effectiveness in adults has been scarcely reported. In this work, we study the role of soybean and fish oil lipid commercial emulsions on inflammatory and profibrotic liver markers in adults with long term PNALD and in in vitro cellular models. Inflammatory and profibrotic markers were measured in serum of ten adults with long term PNALD and in culture supernatants of monocytes. Liver epithelial to mesenchymal transition (EMT) was induced by transforming growth factor beta 1 (TGFβ1) to evaluate in vitro liver fibrosis. Omegaven®, a 100% fish oil commercial emulsion, was infused during four months in two patients with severe long term PNALD reversing, at the first month, the inflammatory, profibrotic and clinical parameters of PNALD. The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced. The other patients under chronic soybean oil-based PN showed elevated inflammatory and profibrotic parameters. In vitro human monocytes stimulated with lipopolysaccharide induced a strong inflammatory response that was suppressed by Omegaven®, but increased by soybean emulsions. In other experiments, TGFβ1 induced EMT that was suppressed by Omegaven® and enhanced by soybean oil lipid emulsions. Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD.

No MeSH data available.


Related in: MedlinePlus