Abstract
Effects of adenoviral infection on in vivo responses to LPS mediated by TNF-alpha were evaluated in a murine model. Adenovirus-infected mice showed decreased mortality from fulminant hepatitis induced by administration of LPS or staphylococcal enterotoxin B in the presence of D-galactosamine. Importantly, TNF-alpha resistance genes within adenoviral E3 region were not required, because E1,E3-deleted vectors showed similar effects. Adenovirus-infected mice exhibited higher TNF-alpha levels after LPS stimulation, no difference in TNFR1 expression, and similar mortality from Fas-induced fulminant hepatitis. Decreased production of IL-6 and KC in response to exogenous TNF-alpha, in addition to protection from TNF-alpha, suggested that adenoviral infection results in TNF-alpha tolerance.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenovirus Infections, Human / immunology*
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Adenovirus Infections, Human / mortality
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Adenoviruses, Human / immunology
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Animals
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Antigens, CD / biosynthesis
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Autoantibodies / toxicity
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Cell Line
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Disease Models, Animal
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Female
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Galactosamine / toxicity
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Humans
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Immune Tolerance / physiology*
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Injections, Intraperitoneal
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Injections, Intravenous
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Lipopolysaccharides / toxicity*
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Liver / immunology
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Liver / metabolism
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Liver / pathology
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Liver Failure / immunology*
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Liver Failure / mortality*
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Liver Failure / pathology
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Liver Failure / prevention & control
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor, Type I
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Survival Analysis
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / physiology*
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Up-Regulation / immunology
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fas Receptor / immunology
Substances
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Antigens, CD
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Autoantibodies
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Lipopolysaccharides
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Tumor Necrosis Factor-alpha
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fas Receptor
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Galactosamine