Endogenous leukemia inhibitory factor attenuates endotoxin response

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-...

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Bibliographic Details
Published in:Laboratory investigation 2005-02, Vol.85 (2), p.276-284
Main Authors: Weber, Marietta A, Schnyder-Candrian, Silvia, Schnyder, Bruno, Quesniaux, Valerie, Poli, Valeria, Stewart, Colin L, Ryffel, Bernhard
Format: Article
Language:English
Subjects:
Acute-Phase Reaction - etiology
Animals
Biological and medical sciences
Biotechnology
Cells, Cultured
Down-Regulation
Endotoxemia - prevention & control
endotoxic shock
Endotoxins - blood
Fundamental and applied biological sciences. Psychology
Galactosamine - administration & dosage
Galactosamine - pharmacology
IL-6, acute phase
Immunology
Interleukin-10 - blood
Interleukin-6 - blood
Interleukin-6 - genetics
Investigative techniques, diagnostic techniques (general aspects)
Leukemia Inhibitory Factor
LIF
LIF-deficient mice
Life Sciences
Lipopolysaccharides - toxicity
Liver - pathology
LPS
Lung - pathology
Macrophages - drug effects
Macrophages - physiology
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Knockout
RNA, Messenger - analysis
Serum Amyloid A Protein - analysis
Shock, Septic - prevention & control
Spleen - pathology
Time Factors
TNF
Tumor Necrosis Factor-alpha - analysis
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary: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.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.3700216