Tolerance to lipopolysaccharide is not related to the ability of the hypothalamus to produce prostaglandin E-2

The effects of repeated administration of Escherichia coti lipopolysaccharide (LPS) on body temperature and hypothalamic prostaglandin E-2 (PGE(2)) 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 PGE(2). 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 PGE(2) production after both the first and second injections of the pyrogen. This Zed us to conclude that endotoxin tolerance is independent of the hypothalamic production of PGE(2) in response to repeated administration of LPS.