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Endogenous leukemia inhibitory factor attenuates endotoxin response
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Journal Article
Endogenous leukemia inhibitory factor attenuates endotoxin response
2005
Overview
Leukemia inhibitory factor (LIF) is induced in inflammation and likely plays a regulatory role. Using LIF-deficient mice (LIF−/−), we report here that endogenous LIF has a protective role in endotoxic shock and host defence. LIF−/− mice have heightened sensitivity to LPS in a LPS/D-galactosamine (D-Gal) sensitization model compared to wild-type mice (LIF+/+), enhanced thrombocytopenia and leukopenia, with increased hepatic necrosis, neutrophil sequestration in the lung and accelerated mortality. These findings correlated with 10-fold higher tumour necrosis factor-α (TNFα) and interleukin-6 (IL-6) serum levels and reduced IL-10 production in LIF−/− mice in response to LPS. Therefore, endogenous LIF attenuates the endotoxic shock response, enhances the expression of basal acute phase proteins and IL-10 production, which downregulates TNFα synthesis and release and thereby confers partial protection to endotoxemia.
Publisher
Elsevier Inc,Nature Publishing Group US,Nature Publishing,Nature Publishing Group,Elsevier (anciennement Nature Publishing Group)
Subject
Acute-Phase Reaction - etiology
/ Animals
/ Biological and medical sciences
/ Endotoxemia - prevention & control
/ Fundamental and applied biological sciences. Psychology
/ Galactosamine - administration & dosage
/ Galactosamine - pharmacology
/ Investigative techniques, diagnostic techniques (general aspects)
/ LIF
/ Lipopolysaccharides - toxicity
/ LPS
/ Medicine
/ Mice
/ Serum Amyloid A Protein - analysis
/ Shock, Septic - prevention & control
/ TNF
