Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice
Paul, L.; Fraifeld, V.; Kaplanski, J.
American Journal of Physiology 276(1): R52-R58
1999
ISSN/ISBN: 0002-9513 PMID: 9887177 Document Number: 505246
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-a (TNF-a), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 mg/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-a 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-a. 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-a bioactivity. Reprinted by permission of the publisher.