Abstract
Tumor necrosis factor (TNF) is a central mediator in lethal shock and an interesting cytokine for anticancer therapy. To inhibit TNF-induced lethal shock, it is important to identify protective genes. Here we demonstrate that the SPRET/Ei mouse strain, derived from Mus spretus, exhibits an extremely dominant resistance to TNF-induced lethal inflammation. An interspecific backcross experiment revealed that the TNF hyporesponse is linked to loci on chromosomes 2, 6, and 11. Treatment of inoculated tumors with TNF and IFN-gamma leads to regression and a highly reduced toxicity in (C57BL/6 x SPRET/Ei)F(1) mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Death / drug effects
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Drug Resistance
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Female
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Genetic Linkage
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Interferon-gamma / therapeutic use
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Interleukin-6 / biosynthesis
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / immunology
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Male
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Melanoma, Experimental / drug therapy
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Muridae
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Recombinant Proteins / therapeutic use
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Recombinant Proteins / toxicity
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Shock / etiology*
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Tumor Necrosis Factor-alpha / therapeutic use
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Tumor Necrosis Factor-alpha / toxicity*
Substances
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Interleukin-6
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Interferon-gamma