Tolerance to lipopolysaccharide is not related to the ability of the hypothalamus to produce prostaglandin E₂

The effects of repeated administration of Escherichia coli lipopolysaccharide (LPS) on body temperature and hypothalamic prostaglandin E₂ (PGE₂) production was examined in male Sprague-Dawley rats to elucidate whether the development;of endotoxin tolerance is related to the ability of the hypothalamus to produce PGE₂. Initial injection of LPS resulted in hyperthermia, preceded by short-termed hypothermia, while no changes in body temperature were observed after the second injection (administered 48 h later). In contrast, LPS induced elevation in hypothalamic PGE₂ production after both the first and second injections of the pyrogen. This led us to conclude that endotoxin tolerance is independent of the hypothalamic production of PGE₂ in response to repeated administration of LPS.