Differential roles of tumor necrosis factor-alpha and interferon-gamma in mouse hypermetabolic and anorectic responses induced by LPS

Autor: Arsenijevic D, Garcia I, Vesin C, Vesin D, Arsenijevic Y, Seydoux J, Girardier L, Ryffel B, Abdul DULLOO, Richard D
Předmět:
Lipopolysaccharides
Male
Transcriptional Activation
Receptors
Tumor Necrosis Factor/genetics
Cytokines/biosynthesis/blood/genetics
Mice
Transgenic
ddc:616.07
Tumor Necrosis Factor-alpha/biosynthesis/genetics/ immunology
Receptors
Tumor Necrosis Factor
Energy Metabolism/drug effects
Eating
Interferon-gamma
Mice
Antigens
CD
Animals
RNA
Messenger
Lymphotoxin-alpha
Lymphotoxin-alpha/genetics/immunology
Receptors
Interferon
Mice
Knockout
Interferon-gamma/biosynthesis/ immunology
Brain/anatomy & histology/drug effects/immunology
Tumor Necrosis Factor-alpha
Evans Blue/metabolism
Receptors
Interferon/genetics
Antigens
CD/genetics
Brain
RNA
Messenger/biosynthesis
Mice
Inbred C57BL
Blood-Brain Barrier
Receptors
Tumor Necrosis Factor
Type I
Spleen/drug effects/immunology
Cytokines
Female
Lipopolysaccharides/ pharmacology
Energy Metabolism
Blood-Brain Barrier/drug effects
Spleen
Evans Blue
Zdroj: Europe PubMed Central
European Cytokine Network, Vol. 11, No 4 (2000) pp. 662-668
ISSN: 1148-5493
Popis: Lipopolysaccharide (LPS)-induced effects on energy balance are characterized by alterations in energy expenditure (hypermetabolism) and food intake (anorexia). To study the role of tumour necrosis factor alpha (TNF-alpha) on some of these metabolic responses to endotoxin, we have used transgenic mice expressing soluble tumour necrosis factor receptor-1 IgG fusion protein (TNFR1-IgG) as well as TNF-alpha knockout (KO), lymphotoxin-alpha (LT-alpha) KO, and interferon-gamma receptor (IFN-gamma R) KO mice. The results from TNFR1-IgG transgenic mice suggest that the hypermetabolic and anorectic responses induced by LPS are independently regulated since, in the absence of TNF-alpha or LT-alpha, the LPS-induced hypermetabolism is almost prevented but not the anorexia. The anorectic response shows the strongest association with IFN-gamma since both IFN-gamma R KO mice and mice treated with anti-IFN-gamma antibody showed marked reduction in the LPS-induced anorexia compared to other mice. IFN-gamma R KO mice also have an attenuated thermogenic response to endotoxin. Anti-Asialo GM1 antibody treatment attenuated both the hypermetabolic and anorectic responses to LPS, to an extent comparable to that observed in IFN-gamma R KO mice. This finding suggests that natural killer cells (lymphocytic subsets) may be involved in IFN-gamma production and play an important role in the metabolic alterations induced by LPS. We also showed that the hypermetabolic response of control mice is associated with an upregulation of cytokine expression within the brain and an increase in permeability of the blood brain barrier. LPS-induced anorexia appears to involve peripheral cytokine expression.
Databáze: OpenAIRE
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