Abstract
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-alpha (TNFalpha) 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 TNFalpha synthesis and release and thereby confers partial protection to endotoxemia.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute-Phase Reaction / etiology
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Animals
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Cells, Cultured
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Down-Regulation
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Endotoxemia / prevention & control*
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Endotoxins / blood*
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Galactosamine / administration & dosage
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Galactosamine / pharmacology
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Interleukin-10 / blood
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Interleukin-6 / blood
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Interleukin-6 / genetics*
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Leukemia Inhibitory Factor
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Lipopolysaccharides / toxicity
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Liver / pathology
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Lung / pathology
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Macrophages / drug effects
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Macrophages / physiology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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RNA, Messenger / analysis
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Serum Amyloid A Protein / analysis
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Shock, Septic / prevention & control*
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Spleen / pathology
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Time Factors
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Tumor Necrosis Factor-alpha / analysis
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
Substances
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Endotoxins
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Interleukin-6
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Leukemia Inhibitory Factor
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Lif protein, mouse
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Lipopolysaccharides
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RNA, Messenger
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Serum Amyloid A Protein
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Galactosamine