Abstract
We here report that administration to mice of WEB2170, a potent platelet-activating factor (PAF) receptor antagonist, prevents both PAF-induced and murine tumor necrosis factor (TNF)-induced lethality in galactosamine (GalN)-sensitized mice. Furthermore, we demonstrate that pretreatment with alpha 1-acid glycoprotein (AGP) or interleukin-1 (IL-1) protects against TNF-induced, but not against PAF-induced lethality. We conclude that PAF is a mediator in TNF/GalN-induced lethal shock, but that the protection conferred by AGP or IL-1 pretreatment is not at the level of scavenging PAF.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Azepines / pharmacology*
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Female
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Galactosamine / pharmacology*
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Interleukin-1 / pharmacology
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Mice
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Mice, Inbred C57BL
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Orosomucoid / pharmacology
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Platelet Activating Factor / antagonists & inhibitors
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Platelet Activating Factor / physiology*
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Platelet Activating Factor / toxicity
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Platelet Aggregation Inhibitors / pharmacology*
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Shock / physiopathology
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Triazoles / pharmacology*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / physiology
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Tumor Necrosis Factor-alpha / toxicity*
Substances
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Azepines
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Interleukin-1
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Orosomucoid
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Platelet Activating Factor
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Platelet Aggregation Inhibitors
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Triazoles
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Tumor Necrosis Factor-alpha
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Galactosamine
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bepafant