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

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The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (T(b)) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in T(b), plasma tumor necrosis factor-α (TNF-α), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 μg/mouse) led to a decrease in T(b) starting i h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF- α 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-α. 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-α bioactivity.

Original languageEnglish
Pages (from-to)R52-R58
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number1 45-1
StatePublished - 1 Jan 1999


  • CD/1 mice
  • Hypothalamic eicosanoids
  • Lipopolysaccharide-induced hypothermia
  • MK-886
  • Tumor necrosis factor- α


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