Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats |
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Authors: | Azab Abed N Kaplanski Jacob |
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Institution: | Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, 84105 Beer-Sheva, Israel. |
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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. |
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