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Open Access 01-10-2011 | Research

mRNA-based approach to monitor recombinant gamma-interferon restoration of LPS-induced endotoxin tolerance

Authors: Fanny Turrel-Davin, Fabienne Venet, Cécile Monnin, Véronique Barbalat, Elisabeth Cerrato, Alexandre Pachot, Alain Lepape, Christine Alberti-Segui, Guillaume Monneret

Published in: Critical Care | Issue 5/2011

Abstract

Introduction

It is now well accepted that sepsis is associated with the development of a pronounced immunosuppressive state, characterized by severe immune alterations (e.g. reduced proliferative capacity, endotoxin tolerance, apoptosis) participating in increased mortality and susceptibility to nosocomial infections. Efforts are currently aimed at restoring a functional immune response in septic patients. Successful therapy depends on the identification of appropriate immunostimulatory drugs and on the development of suitable biomarkers that could be used to stratify patients and to follow response to treatment.

Methods

In this study, we evaluated the ex vivo effect of recombinant interferon gamma (rIFN-γ) in restoring monocyte functionality (endotoxin-induced Tumor Necrosis Factor-α production) in a two-hit model of endotoxin tolerance (ET) with peripheral blood mononuclear cells from healthy volunteers and in whole blood of septic shock patients. Importantly, we used quantitative-reverse transcription polymerase-chain reaction to monitor the effect of rIFN-γ on the expression of seven genes known to participate in ET (TNF-α, IL-10, HLA-DRA, CIITA, IRAK-M, ABIN-3 and LY64).

Results

Expression analysis of those genes confirmed the presence of an immunosuppression state and the ex vivo restoration of immune functions by rIFN-γ. We show for the first time that rIFN-γ is able to bypass, at the mRNA level, the effect of negative regulators of the LPS signalling pathway such as IRAK-M, ABIN-3 and LY 64.

Conclusions

Overall, mRNA expressions of a panel of genes could represent promising candidates for the ex vivo evaluation of rIFN-γ effect on monocyte functionality. This ex vivo translational research study demonstrates the potential of a mRNA-based approach to successfully monitor drug efficacy.

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Title: mRNA-based approach to monitor recombinant gamma-interferon restoration of LPS-induced endotoxin tolerance
Authors: Fanny Turrel-Davin
Fabienne Venet
Cécile Monnin
Véronique Barbalat
Elisabeth Cerrato
Alexandre Pachot
Alain Lepape
Christine Alberti-Segui
Guillaume Monneret
Publication date: 01-10-2011
Publisher: BioMed Central
Published in: Critical Care / Issue 5/2011
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc10513

Keynote webinar | Spotlight on medication adherence

Springer Medicine

mRNA-based approach to monitor recombinant gamma-interferon restoration of LPS-induced endotoxin tolerance

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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