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Published on: February 20, 2015
Interleukin-10 controls the protective effects of circulating microparticles from patients with septic shock on
Hadj Ahmed Mostefai1, Jean-Michel Bourget, Ferhat Meziani
1LUNAM Université, INSERM UMR U1063, Université d’Angers, Angers, France.
Abstract:
During sepsis, inflammation can be orchestrated by the interaction between circulating and vascular cells that, under activation, release MPs (microparticles). Previously, we reported that increased circulating MPs in patients with sepsis play a pivotal role in ex vivo vascular function suggesting that they are protective against vascular hyporeactivity. The present study was designed to investigate the effects of MPs from patients with sepsis on the contractile response of TEVM (tissue-engineered vascular media). TEVM that were composed only of a media layer were produced by tissue engineering from human arterial SMCs (smooth muscle cells) isolated from umbilical cords. TEVM was incubated with MPs isolated from whole blood of 16 patients with sepsis. TEVM were incubated for 24 h with MPs and used for the study of vascular contraction, direct measurements of NO and O2- (superoxide anion) production by EPR and quantification of mRNA cytokine expression. MPs from patients with sepsis increased contraction induced by histamine in TEVM. This effect was not associated with inflammation, neither linked to the activation of NF-κB (nuclear factor κB) pathway nor to the increase in iNOS (inducible NO synthase) and COX (cyclo-oxygenase)-2 expression. In contrast, mRNA expression of IL (interleukin)-10 was enhanced. Then, we investigated the effect of IL-10 on vascular hyporeactivity induced by LPS (lipopolysaccharide). Although IL-10 treatment did not modify the contractile response in TEVM by itself, this interleukin restored contraction in LPS-treated TEVM. In addition, IL-10 treatment both prevented vascular hyporeactivity induced by LPS injection in mice and improved survival of LPS-injected mice. These findings show an association between the capacity of MPs from patients with sepsis to restore vascular hyporeactivity induced by LPS and their ability to increase IL-10 in the tissue-engineered blood vessel model.
Insights
Microparticles (MPs) from sepsis patients restore vascular function by increasing interleukin-10 (IL-10). This finding suggests MPs are protective against sepsis-induced vascular hyporeactivity and improve survival.
Area of Science:
- Vascular Biology
- Immunology
- Sepsis Pathophysiology
Background:
- Sepsis involves complex cell interactions leading to microparticle (MP) release.
- Previously reported protective role of MPs against vascular hyporeactivity in sepsis patients.
- Need to investigate MP effects on vascular contractility and underlying mechanisms.
Purpose of the Study:
- To investigate the effects of sepsis-derived MPs on tissue-engineered vascular media (TEVM) contractility.
- To explore the role of interleukin-10 (IL-10) in MP-mediated vascular responses.
- To assess the therapeutic potential of IL-10 in sepsis-induced vascular dysfunction.
Main Methods:
- TEVM created from human umbilical cord smooth muscle cells.
- Incubation of TEVM with MPs from sepsis patients.
- Measurement of vascular contraction, nitric oxide (NO) and superoxide anion (O2-) production, and cytokine mRNA expression.
- In vivo studies using lipopolysaccharide (LPS)-injected mice to evaluate IL-10 effects.
Main Results:
- Sepsis MPs enhanced histamine-induced contraction in TEVM without increasing inflammation markers.
- MP incubation led to increased interleukin-10 (IL-10) mRNA expression.
- IL-10 treatment restored vascular contractility in LPS-treated TEVM and mice.
- IL-10 administration improved survival in LPS-injected mice.
Conclusions:
- MPs from sepsis patients can restore vascular hyporeactivity, mediated by increased IL-10.
- IL-10 emerges as a key factor in the protective vascular effects of sepsis MPs.
- These findings highlight a potential therapeutic strategy targeting IL-10 for sepsis-induced vascular dysfunction.
