title: Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats.
abstract: Hypothermia is one of the prominent features of the acute phase response to endotoxin (LPS). This study was undertaken to elucidate the effects of the COX-inhibitor Indomethacin (INDO) and the selective FLAP inhibitor MK-886 on LPS-induced hypothermia, mortality and increase in production of hypothalamic prostaglandin E(2) (PGE(2)) and leukotriene during endotoxemia. It has been demonstrated that INDO and MK-886 significantly attenuate the hypothermia induced by LPS, but MK-886 has a lesser (protective) effect than INDO. Only INDO was found to attenuate significantly the hyperthermic response to LPS. Furthermore, INDO significantly reduced the elevation in hypothalamic PGE(2) levels. MK-886 significantly reduced the elevation in hypothalamic leukotriene production only when LPS was given in a dose of 1mg/kg. Both drugs failed to reduce the elevation in plasma TNF-alpha and mortality induced by LPS. We conclude that in rats, febrile response to endotoxin involves many inflammatory mediators. However, it seems that PGE(2) and leukotrienes do not have a pivotal role in the mechanism of LPS-induced mortality.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, 84105 Beer-Sheva, Israel.
authors.forename: Abed N
authors.initials: AN
authors.lastname: Azab
authors.forename: Jacob
authors.initials: J
authors.lastname: Kaplanski
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000378:metabolism*; D019446:Endotoxemia / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism*; D005334:Fever / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D002722:Chlorobenzenes
chemical_list: D015777:Eicosanoids; D007211:Indoles; D007213:Indomethacin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C060893:MK-886; D002722:Chlorobenzenes