Effect of indomethacin on the response of mice to endotoxin.
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Biomedical subjects
Publications and source records attributed to R N Moore.
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Mice infected with a standard challenge of Salmonella typhimurium manifest a number of changes associated with endotoxemia. These changes result in profound alterations in the nutritional and metabolic status of the host. Food and water intake approaches levels of total inanition, blood glucose declines more rapidly than in fasted controls, hepatic phosphoenolpyruvate carboxykinase (the enzyme that is rate limiting in gluconeogenesis) shows diminished activity and loss of cortisol inducibility, and hypothermia, rather than hyperthermia, becomes acute. These changes occur at a time when bacteremia is first demonstrable. This occurs on the 3rd day after infection under the conditions employed. Death occurs in most mice within the next 24 to 48 hr. Mice vaccinated with a highly immunogenic ribosomal preparation and subsequently infected with the standard number of organisms did not manifest the above changes. Other work from this laboratory has established that effects of the type described are elicited by bacterial endotoxin as a result of mediating substances released into the blood by cells of the reticuloendothelial system. Presumably these substances appear in blood of infected mice as well.
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Corticosteroid induction of mouse hepatic phosphoenolpyruvate carboxykinase was inhibited by prior injection of poly I:C. Mice challenged with a lethal dose of endotoxin 4 h after administration of poly I: C could not be protected by a concurrent injection of hydrocortisone.
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