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.
Paul
L
L
Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Fraifeld
V
V
Kaplanski
J
J
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis; D007031:Hypothalamus / Q000378:metabolism; D007035:Hypothermia / Q000209:etiology* / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D015289:Leukotrienes / Q000096:biosynthesis / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D002722:Chlorobenzenes
D015232:Dinoprostone; D007211:Indoles; D015289:Leukotrienes; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C060893:MK-886; D002722:Chlorobenzenes