Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats

Abed N. Azab; Jacob Kaplanski

doi:10.1016/j.plefa.2003.08.005

Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats

Abed N. Azab, Jacob Kaplanski

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16 Scopus citations

Abstract

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 E₂ (PGE₂) 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 PGE₂ levels. MK-886 significantly reduced the elevation in hypothalamic leukotriene production only when LPS was given in a dose of 1 mg/kg. Both drugs failed to reduce the elevation in plasma TNF-α and mortality induced by LPS. We conclude that in rats, febrile response to endotoxin involves many inflammatory mediators. However, it seems that PGE₂ and leukotrienes do not have a pivotal role in the mechanism of LPS-induced mortality.

Original language	English
Pages (from-to)	67-75
Number of pages	9
Journal	Prostaglandins Leukotrienes and Essential Fatty Acids
Volume	70
Issue number	1
DOIs	https://doi.org/10.1016/j.plefa.2003.08.005
State	Published - 1 Jan 2004

Keywords

Cyclooxygenase
FLAP
Fever
Lipooxygenase

ASJC Scopus subject areas

Clinical Biochemistry
Cell Biology

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10.1016/j.plefa.2003.08.005

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title = "Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats",

abstract = "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 E2 (PGE2) 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 PGE2 levels. MK-886 significantly reduced the elevation in hypothalamic leukotriene production only when LPS was given in a dose of 1 mg/kg. Both drugs failed to reduce the elevation in plasma TNF-α and mortality induced by LPS. We conclude that in rats, febrile response to endotoxin involves many inflammatory mediators. However, it seems that PGE2 and leukotrienes do not have a pivotal role in the mechanism of LPS-induced mortality.",

keywords = "Cyclooxygenase, FLAP, Fever, Lipooxygenase",

author = "Azab, {Abed N.} and Jacob Kaplanski",

note = "Funding Information: This research was partially supported by grant No. 98-00434 from United States–Israel Binational Science Foundation (BSF), Jerusalem, Israel.",

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AU - Azab, Abed N.

AU - Kaplanski, Jacob

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PY - 2004/1/1

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N2 - 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 E2 (PGE2) 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 PGE2 levels. MK-886 significantly reduced the elevation in hypothalamic leukotriene production only when LPS was given in a dose of 1 mg/kg. Both drugs failed to reduce the elevation in plasma TNF-α and mortality induced by LPS. We conclude that in rats, febrile response to endotoxin involves many inflammatory mediators. However, it seems that PGE2 and leukotrienes do not have a pivotal role in the mechanism of LPS-induced mortality.

AB - 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 E2 (PGE2) 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 PGE2 levels. MK-886 significantly reduced the elevation in hypothalamic leukotriene production only when LPS was given in a dose of 1 mg/kg. Both drugs failed to reduce the elevation in plasma TNF-α and mortality induced by LPS. We conclude that in rats, febrile response to endotoxin involves many inflammatory mediators. However, it seems that PGE2 and leukotrienes do not have a pivotal role in the mechanism of LPS-induced mortality.

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Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats

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Keywords

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