We examined the kinetics of tumor necrosis factor (TNF) production induced by Escherichia coli lipopolysaccharide (LPS) in relation to LPS tolerance and endotoxemic lesions of piglets. The plasma of piglets demonstrated cytotoxicity to TNF-sensitive L929 cells between 0.5 and 4 h after inoculation with 200 μg kg -1 of LPS. This cytotoxicity was neutralized by anti-bovine TNF serum. These piglets had disseminated intravascular coagulation (DIC) and meningoencephalitis. However, if piglets were first treated with three doses of 40 μg kg -1 of LPS, both TNF production and the occurrence of DIC were inhibited when 200 μg kg -1 of LPS was inoculated into these piglets. Repetitive inoculation with increasing doses of LPS induced fibrinoid vasculitis, meningoencephalitis and pneumonitis, while hemorrhage was minimal. A very low amount of TNF activity was detected from most of the samples of a piglet after repeated LPS inoculation. These results suggested that severity of the hemorrhagic and thrombotic lesions might relate to the amount of endogenous TNF activity, and that LPS tolerance might relate to inhibition of TNF production.
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