l-663536 has been researched along with Hypothermia* in 2 studies
2 other study(ies) available for l-663536 and Hypothermia
Article | Year |
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Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats.
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. Topics: Animals; Body Temperature; Dose-Response Relationship, Drug; Eicosanoids; Endotoxemia; Fever; Hypothermia; Indoles; Indomethacin; Lipopolysaccharides; Male; Rats; Rats, Sprague-Dawley; Survival Rate; Time Factors; Tumor Necrosis Factor-alpha | 2004 |
Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice.
The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-alpha (TNF-alpha), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 microgramg/mouse) led to a decrease in Tb starting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-alpha level in plasma and in LT and PGE2 production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-alpha. MK-886 significantly inhibited LT and enhanced PGE2 production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-alpha bioactivity. Topics: Animals; Body Temperature; Dinoprostone; Hypothalamus; Hypothermia; Indoles; Leukotrienes; Lipopolysaccharides; Lipoxygenase Inhibitors; Male; Mice; Mice, Inbred Strains; Tumor Necrosis Factor-alpha | 1999 |