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Am J Physiol Regul Integr Comp Physiol 276: R52-R58, 1999;
0363-6119/99 $5.00
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Vol. 276, Issue 1, R52-R58, January 1999

Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice

Lada Paul, Vadim Fraifeld, and Jacob Kaplanski

Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel

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 µg/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.

lipopolysaccharide-induced hypothermia; MK-886; tumor necrosis factor-alpha ; hypothalamic eicosanoids; CD/1 mice


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